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
RS_2024_02	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 promotes DNA damage repair in osteoarthritis chondrocytes by activating the Keap1/Nrf2/HO-1 signaling pathway.
Title: Sirt6 promotes DNA damage repair in osteoarthritis chondrocytes by activating the Keap1/Nrf2/HO-1 signaling pathway.
Hepatic Sirt6 activation abrogates acute liver failure.
Title: Hepatic Sirt6 activation abrogates acute liver failure.
Cardiac injury activates STING signaling via upregulating SIRT6 in macrophages after myocardial infarction.
Title: Cardiac injury activates STING signaling via upregulating SIRT6 in macrophages after myocardial infarction.
SIRT6 deficiency causes ovarian hypoplasia by affecting Plod1-related collagen formation.
Title: SIRT6 deficiency causes ovarian hypoplasia by affecting Plod1-related collagen formation.
The transcription factor GATA6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting the role of anti-aging factor SIRT6 and impeding DNA damage repair.
Title: The transcription factor GATA6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting the role of anti-aging factor SIRT6 and impeding DNA damage repair.
Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling.
Title: Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling.
G9a and Sirtuin6 epigenetically modulate host cholesterol accumulation to facilitate mycobacterial survival.
Title: G9a and Sirtuin6 epigenetically modulate host cholesterol accumulation to facilitate mycobacterial survival.
SIRT6 mediated histone H3K9ac deacetylation involves myocardial remodelling through regulating myocardial energy metabolism in TAC mice.
Title: SIRT6 mediated histone H3K9ac deacetylation involves myocardial remodelling through regulating myocardial energy metabolism in TAC mice.
Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice.
Title: Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice.
Sirt6 enhances macrophage lipophagy and improves lipid metabolism disorder by regulating the Wnt1/beta-catenin pathway in atherosclerosis.
Title: Sirt6 enhances macrophage lipophagy and improves lipid metabolism disorder by regulating the Wnt1/β-catenin pathway in atherosclerosis.

Submit: New GeneRIF Correction See all GeneRIFs (192)

Variation

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Alleles

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

Endonuclease-mediated (5)
Targeted (9) 1 citation

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

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
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
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 demyristoylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein depalmitoylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein lysine deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent protein lysine deacetylase 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 glycosyltransferase activity	IEA Inferred from Electronic Annotation more info
enables lncRNA binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation 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
enables transcription corepressor activity	IGI Inferred from Genetic Interaction more info	PubMed
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
acts_upstream_of_or_within DNA repair	IEA Inferred from Electronic Annotation more info
involved_in DNA repair-dependent chromatin remodeling	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 chromatin remodeling	ISO Inferred from Sequence Orthology 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 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
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 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 insulin secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
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 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 retrotransposon silencing	IDA Inferred from Direct Assay more info	PubMed
involved_in retrotransposon silencing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in subtelomeric heterochromatin formation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
part_of 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
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
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	ISO Inferred from Sequence Orthology more info
part_of 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

Names: NAD-dependent deacetylase sirtuin-6; NAD-dependent protein 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: GCF_000001635.27-RS_2024_02

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 deacylase 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+, ...