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
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; AI043036; 2810449N18Rik
Expression: Ubiquitous expression in thymus adult (RPKM 15.8), ovary adult (RPKM 15.8) and 28 other tissues See more
Orthologs: human all

Genomic context

Location:: 10 C1; 10 39.72 cM

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
108.20200622	current	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (81621787..81627792, complement)
Build 37.2	previous assembly	MGSCv37 (GCF_000001635.18)	10	NC_000076.5 (81084531..81090353, complement)

Chromosome 10 - NC_000076.6 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?

Our study provides in vivo evidence that ECs undergo EndMT during vascular aging, which increases endothelial permeability. SIRT6-mediated transcriptional suppression of MALAT1 is a key mechanism for EndMT. Manipulating EndMT may be considered as a new therapeutic strategy for retarding aging-associated vascular diseases
Title: SIRT6-mediated transcriptional suppression of MALAT1 is a key mechanism for endothelial to mesenchymal transition.
the abundance of acetylated XBP1s and concordant hepatic steatosis were increased in hepatocyte-specific Sirt6 knockout and obese mice but were decreased by genetic overexpression and pharmacological activation of Sirt6.
Title: Deacetylation of XBP1s by sirtuin 6 confers resistance to ER stress-induced hepatic steatosis.
Adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue.
Title: Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans.
The Nampt-Sirt6 axis in proximal kidney tubules serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy.
Title: Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy.
hepatic Sirt6 downregulates the ERalpha protein level in a p300-dependent manner.
Title: Sirt6 deletion in hepatocytes increases insulin sensitivity of female mice by enhancing ERα expression.
Depletion of SIRT6 in oocytes induces dysfunctional telomeres and apoptosis of the resultant early embryos, leading to developmental delay and cytoplasmic fragmentation. Importantly, we further find that overexpression of SIRT6 in aged oocytes promotes the telomere elongation in 2-cell embryos and lowers the incidence of apoptotic blastomeres.
Title: SIRT6 participates in the quality control of aged oocytes via modulating telomere function.
Overexpression of SIRT6 can protect kidney epithelial cell damage of acute kidney injury by inhibiting apoptosis and inducing autophagy, which might become a new approach to the treatment of acute kidney injury.
Title: Sirtuin 6 overexpression relieves sepsis-induced acute kidney injury by promoting autophagy.
Authors found that loss of function of Sirt6 could significantly decrease reprogramming efficiency and showed that Sirt6-null iPS-like cell line has intrinsically a differentiation defect even though the establishment of normal self-renewal.
Title: Sirt6 regulates efficiency of mouse somatic reprogramming and maintenance of pluripotency.
SIRT6 overexpression inhibits cementogenesis by suppressing the activity of glucose transporter 1.
Title: SIRT6 overexpression inhibits cementogenesis by suppressing glucose transporter 1.
Collectively, our studies for the first time demonstrate that SIRT6 prevents pathological hypertension and its complications by maintaining endothelial function, at least in part, through epigenetic regulation of Nkx3.2-mediated GATA5 signaling suggesting that SIRT6 may be an innovative therapeutic strategy for treating patients with hypertension.
Title: Endothelial SIRT6 Is Vital to Prevent Hypertension and Associated Cardiorenal Injury Through Targeting Nkx3.2-GATA5 Signaling.

Submit: New GeneRIF Correction See all GeneRIFs (109)

Variation

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Alleles

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

Targeted (8) 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

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: 315 organisms have orthologs with human gene Sirt6
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
NAD(P)+-protein-arginine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
NAD+ binding	IEA Inferred from Electronic Annotation more info
NAD-dependent histone deacetylase activity (H3-K9 specific)	IBA Inferred from Biological aspect of Ancestor more info	PubMed
NAD-dependent histone deacetylase activity (H3-K9 specific)	IMP Inferred from Mutant Phenotype more info	PubMed
NAD-dependent histone deacetylase activity (H3-K9 specific)	ISO Inferred from Sequence Orthology more info
NAD-dependent histone deacetylase activity (H3-K9 specific)	TAS Traceable Author Statement more info
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
deacetylase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
histone deacetylase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein deacetylase activity	ISO Inferred from Sequence Orthology more info
transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcription corepressor activity	IGI Inferred from Genetic Interaction more info	PubMed
transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
base-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
histone H3 deacetylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of glucose import	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of glycolytic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation blood vessel branching	ISO Inferred from Sequence Orthology more info
positive regulation of chondrocyte proliferation	ISO Inferred from Sequence Orthology more info
positive regulation of chromatin silencing at telomere	ISO Inferred from Sequence Orthology more info
positive regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of telomere maintenance	ISO Inferred from Sequence Orthology more info
positive regulation of telomeric heterochromatin assembly	ISO Inferred from Sequence Orthology more info
positive regulation of transcription factor catabolic process	ISO Inferred from Sequence Orthology more info
positive regulation of vascular endothelial cell proliferation	ISO Inferred from Sequence Orthology more info
post-embryonic cardiac muscle cell growth involved in heart morphogenesis	ISO Inferred from Sequence Orthology more info
protein ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
protein deacetylation	IMP Inferred from Mutant Phenotype more info	PubMed
protein deacetylation	ISO Inferred from Sequence Orthology more info
protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of double-strand break repair via homologous recombination	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
chromosome, subtelomeric region	ISO Inferred from Sequence Orthology more info
cytoplasm	ISO Inferred from Sequence Orthology more info
nucleoplasm	ISO Inferred from Sequence Orthology more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: NAD-dependent protein deacetylase sirtuin-6

Names: NAD-dependent deacetylase sirtuin-6; SIR2-like protein 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 deacetylase 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

ENSMUSP00000113953.1, ENSMUST00000119324.7

Conserved Domains (1) summary

cd01410
Location:5 → 217

SIRT7; 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 ...
NM_001378944.1 → NP_001365873.1 NAD-dependent protein deacetylase sirtuin-6 isoform 1

Status: VALIDATED

Description

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

Source sequence(s)

AC153919
NM_001378945.1 → NP_001365874.1 NAD-dependent protein deacetylase sirtuin-6 isoform 2

Status: VALIDATED

Description

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

Source sequence(s)

AC153919
NM_181586.4 → NP_853617.1 NAD-dependent protein deacetylase 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

ENSMUSP00000048971.8, ENSMUST00000042923.8

Conserved Domains (1) summary

cd01410
Location:45 → 257

SIRT7; 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 ...

RNA

NR_166193.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC153919

RefSeqs of Annotated Genomes: Mus musculus Updated Annotation Release 108.

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

Reference GRCm38.p6 C57BL/6J

Genomic

NC_000076.6 Reference GRCm38.p6 C57BL/6J

Range

81621787..81627792 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011243507.3 → XP_011241809.1 NAD-dependent protein deacetylase sirtuin-6 isoform X2

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+, ...