Sirt6 sirtuin 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Sirt6provided by MGI
Official Full Name: sirtuin 6provided by MGI
Primary source: MGI:MGI:1354161
See related: Ensembl:ENSMUSG00000034748 AllianceGenome:MGI:1354161
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Sir2l6; mSIRT6; 2810449N18Rik
Summary: Enables several functions, including NAD(P)+-protein-arginine ADP-ribosyltransferase activity; NAD-dependent histone deacetylase activity (H3-K9 specific); and transcription corepressor activity. Involved in several processes, including cellular protein modification process; negative regulation of nucleobase-containing compound metabolic process; and positive regulation of cell population proliferation. Located in nucleus. Is expressed in several structures, including alimentary system; central nervous system; gonad; musculature; and retina. Used to study progeria. Orthologous to human SIRT6 (sirtuin 6). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in thymus adult (RPKM 15.8), ovary adult (RPKM 15.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 C1; 10 39.72 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (81457621..81463631, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (81621787..81627792, complement)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SIRT6 regulates endothelium-dependent relaxation by modulating nitric oxide synthase 3 (NOS3).
Title: SIRT6 regulates endothelium-dependent relaxation by modulating nitric oxide synthase 3 (NOS3).
Astrocytic SIRT6 is a potential anti-depression and anti-anxiety target.
Title: Astrocytic SIRT6 is a potential anti-depression and anti-anxiety target.
SIRT6 is a key regulator of mitochondrial function in the brain.
Title: SIRT6 is a key regulator of mitochondrial function in the brain.
Endothelial SIRT6 deficiency promotes arterial thrombosis in mice.
Title: Endothelial SIRT6 deficiency promotes arterial thrombosis in mice.
BMSC-Derived Exosomal Egr2 Ameliorates Ischemic Stroke by Directly Upregulating SIRT6 to Suppress Notch Signaling.
Title: BMSC-Derived Exosomal Egr2 Ameliorates Ischemic Stroke by Directly Upregulating SIRT6 to Suppress Notch Signaling.
Sirt6 mediates antioxidative functions by increasing Nrf2 abundance.
Title: Sirt6 mediates antioxidative functions by increasing Nrf2 abundance.
Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation.
Title: Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation.
SIRT6 Protects Against Myocardial Ischemia-Reperfusion Injury by Attenuating Aging-Related CHMP2B Accumulation.
Title: SIRT6 Protects Against Myocardial Ischemia-Reperfusion Injury by Attenuating Aging-Related CHMP2B Accumulation.
Phosphorylation by GSK-3beta increases the stability of SIRT6 to alleviate TGF-beta-induced fibrotic response in renal tubular cells.
Title: Phosphorylation by GSK-3β increases the stability of SIRT6 to alleviate TGF-β-induced fibrotic response in renal tubular cells.
Sirt6 deficiency contributes to mitochondrial fission and oxidative damage in podocytes via ROCK1-Drp1 signalling pathway.
Title: Sirt6 deficiency contributes to mitochondrial fission and oxidative damage in podocytes via ROCK1-Drp1 signalling pathway.

Submit: New GeneRIF Correction See all GeneRIFs (171)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (9) 1 citation
Endonuclease-mediated (3)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI043036 (e-PCR)
- UniSTS:165713

Sirt6 (e-PCR), detects polymorphism
- UniSTS:531299

Sirt6 (e-PCR), detects polymorphism
- UniSTS:531300

NoName (e-PCR)
- UniSTS:236417

Homology

Homologs of the Sirt6 gene: The Sirt6 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, fruit fly, mosquito, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 488 organisms have orthologs with human gene Sirt6
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA damage sensor activity	ISO Inferred from Sequence Orthology more info
enables NAD+ binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables NAD+-protein ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein ADP-ribosyltransferase activity	ISO Inferred from Sequence Orthology more info
enables NAD+-protein-arginine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent histone H3K18 deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent histone H3K18 deacetylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent histone H3K56 deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent histone H3K56 deacetylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent histone H3K9 deacetylase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables NAD-dependent histone H3K9 deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent histone H3K9 deacetylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NAD-dependent histone H3K9 deacetylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent histone H3K9 deacetylase activity	TAS Traceable Author Statement more info
enables NAD-dependent histone deacetylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent protein deacetylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein demyristoylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein depalmitoylase activity	ISO Inferred from Sequence Orthology more info
enables RNA binding	IEA Inferred from Electronic Annotation more info
enables TORC2 complex binding	IDA Inferred from Direct Assay more info	PubMed
enables acyltransferase activity	IEA Inferred from Electronic Annotation more info
enables chromatin DNA binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables damaged DNA binding	ISO Inferred from Sequence Orthology more info
enables enzyme activator activity	ISO Inferred from Sequence Orthology more info
enables glycosyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone deacetylase regulator activity	ISO Inferred from Sequence Orthology more info
enables lncRNA binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables molecular function activator activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular function activator activity	ISO Inferred from Sequence Orthology more info
enables nucleosome binding	ISO Inferred from Sequence Orthology more info
enables nucleotidyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein lysine deacetylase activity	ISO Inferred from Sequence Orthology more info
enables transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables transcription corepressor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables transcription regulator inhibitor activity	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in base-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac muscle cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chromatin organization	IEA Inferred from Electronic Annotation more info
involved_in circadian regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of adult lifespan	ISO Inferred from Sequence Orthology more info
involved_in double-strand break repair	ISO Inferred from Sequence Orthology more info
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in histone deacetylation	ISO Inferred from Sequence Orthology more info
involved_in ketone biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cellular senescence	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of gene expression, epigenetic	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of gluconeogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of glucose import	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of glycolytic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of glycolytic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein import into nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein localization to chromatin	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of transcription elongation by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transposition	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transposition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pericentric heterochromatin formation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of blood vessel branching	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chondrocyte proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of double-strand break repair	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fat cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of histone deacetylase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of insulin secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein export from nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein export from nucleus	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein localization to chromatin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of stem cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of stem cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of stem cell population maintenance	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomere maintenance	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription factor catabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular endothelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in post-embryonic cardiac muscle cell growth involved in heart morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in protein deacetylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein deacetylation	ISO Inferred from Sequence Orthology more info
involved_in protein delipidation	ISO Inferred from Sequence Orthology more info
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein destabilization	ISO Inferred from Sequence Orthology more info
involved_in protein localization to site of double-strand break	ISO Inferred from Sequence Orthology more info
involved_in regulation of circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of double-strand break repair via homologous recombination	ISO Inferred from Sequence Orthology more info
involved_in regulation of lipid catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of lipid metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein secretion	ISO Inferred from Sequence Orthology more info
involved_in response to UV	ISO Inferred from Sequence Orthology more info
involved_in subtelomeric heterochromatin formation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in chromatin	IDA Inferred from Direct Assay more info	PubMed
is_active_in chromatin	ISO Inferred from Sequence Orthology more info
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in chromosome, subtelomeric region	ISO Inferred from Sequence Orthology more info
located_in chromosome, telomeric region	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in pericentric heterochromatin	ISO Inferred from Sequence Orthology more info
is_active_in site of DNA damage	ISO Inferred from Sequence Orthology more info
is_active_in site of double-strand break	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: NAD-dependent protein deacylase sirtuin-6; NAD-dependent protein deacetylase sirtuin-6

Names: NAD-dependent deacetylase sirtuin-6; SIR2-like protein 6; protein mono-ADP-ribosyltransferase sirtuin-6; regulatory protein SIR2 homolog 6

NP_001156902.1

EC 2.3.1.286

NP_001365873.1

EC 2.3.1.286

NP_001365874.1

EC 2.3.1.286

NP_853617.1

EC 2.3.1.286

XP_011241809.1

EC 2.3.1.286

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_001163430.2 → NP_001156902.1 NAD-dependent protein deacylase sirtuin-6 isoform 2

See identical proteins and their annotated locations for NP_001156902.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the UTRs and 5' coding region and initiates translation at a downstream start codon, compared to variant 1. The resulting isoform (2) has a shorter N-terminus compared to isoform 1. Variants 2 and 4 both encode the same isoform (2).

Source sequence(s)

AC153919

Consensus CDS

CCDS48645.1

UniProtKB/TrEMBL

Q3UKP1

Related

ENSMUSP00000113953.2, ENSMUST00000119324.8

Conserved Domains (1) summary

cd01410
Location:5 → 217

SIRT7; Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein ...
NM_001378944.1 → NP_001365873.1 NAD-dependent protein deacylase sirtuin-6 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (3), as well as variant 1, encodes isoform 1.

Source sequence(s)

AC153919

UniProtKB/Swiss-Prot

P59941

Conserved Domains (1) summary

cd01410
Location:45 → 257

SIRT7; Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein ...
NM_001378945.1 → NP_001365874.1 NAD-dependent protein deacylase sirtuin-6 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (4), as well as variant 2, encodes isoform 2.

Source sequence(s)

AC153919

UniProtKB/TrEMBL

Q3UKP1

Conserved Domains (1) summary

cd01410
Location:5 → 217

SIRT7; Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein ...
NM_181586.4 → NP_853617.1 NAD-dependent protein deacylase sirtuin-6 isoform 1

See identical proteins and their annotated locations for NP_853617.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1 and 3 both encode the same isoform (1).

Source sequence(s)

AC153919

Consensus CDS

CCDS24066.1

UniProtKB/Swiss-Prot

P59941

Related

ENSMUSP00000048971.9, ENSMUST00000042923.9

Conserved Domains (1) summary

cd01410
Location:45 → 257

SIRT7; Eukaryotic and prokaryotic group (class4) which includes human sirtuin SIRT6, SIRT7, and several bacterial homologs; and are members of the SIR2 family of proteins, silent information regulator 2 (Sir2) enzymes which catalyze NAD+-dependent protein ...

RNA

NR_166193.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC153919

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000076.7 Reference GRCm39 C57BL/6J

Range

81457621..81463631 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011243507.4 → XP_011241809.1 NAD-dependent protein deacetylase sirtuin-6 isoform X1

Conserved Domains (1) summary

cl00195
Location:101 → 261

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+, ...