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 Vega:OTTMUSG00000030471
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:: 10

Annotation release	Status	Assembly	Chr	Location
106	current	GRCm38.p4 (GCF_000001635.24)	10	NC_000076.6 (81621786..81627797, 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 FunctionsWhat's a GeneRIF?

SIRT6 knockout cells resist apoptosis initiation but not progression.
Title: SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis.
Sirt6 in pancreatic beta cells deacetylates FoxO1 and subsequently increases the expression of Pdx1 and Glut2 to maintain the glucose-sensing ability of pancreatic beta cells and systemic glucose tolerance.
Title: Insulin secretion impairment in Sirt6 knockout pancreatic β cells is mediated by suppression of the FoxO1-Pdx1-Glut2 pathway.
SIRT6 interacts with and promotes phospho-ATF2 binding to the PGC-1alpha gene promoter to activate its expression. The present study reveals a critical role for SIRT6 in regulating thermogenesis of fat.
Title: Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat.
p53-dependent SIRT6 expression protects cells from Abeta42-induced DNA damage.
Title: p53-dependent SIRT6 expression protects Aβ42-induced DNA damage.
Moreover, the authors showed that Sirt6, induced by RANKL-dependent NFATc1 expression, forms a complex with B lymphocyte-induced maturation protein-1 (Blimp1) to negatively regulate expression of anti-osteoclastogenic gene such as Mafb.
Title: Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation.
Collectively, our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-beta induced RPE dysfunction.
Title: Autophagy activated by SIRT6 regulates Aβ induced inflammatory response in RPEs.
Sirt6 inhibits Notch1 and Notch4 transcription by deacetylating histone H3K9.
Title: Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.
Sirt6 is downregulated in induced pluripotent stem cells from old mice.
Title: Sirt6 Promotes DNA End Joining in iPSCs Derived from Old Mice.
post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of double-strand break.
Title: JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks.
These findings reveal a crucial role of SIRT6 in adipogenesis and provide potential therapeutic targets for obesity.
Title: SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion.

Submit: New GeneRIF Correction See all GeneRIFs (74)

Variation

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Alleles

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

Targeted (7) 1 citation

Pathways from BioSystems

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Central carbon metabolism in cancer, organism-specific biosystem (from KEGG)
Central carbon metabolism in cancer, organism-specific biosystemMalignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamen...
Central carbon metabolism in cancer, conserved biosystem (from KEGG)
Central carbon metabolism in cancer, conserved biosystemMalignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamen...
DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
DNA Double-Strand Break Repair, organism-specific biosystemcomputationally inferred pathway (not manually curated)
DNA Repair, organism-specific biosystem (from REACTOME)
DNA Repair, organism-specific biosystemcomputationally inferred pathway (not manually curated)
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystemcomputationally inferred pathway (not manually curated)
Homology Directed Repair, organism-specific biosystem (from REACTOME)
Homology Directed Repair, organism-specific biosystemcomputationally inferred pathway (not manually curated)
Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
Processing of DNA double-strand break ends, organism-specific biosystemcomputationally inferred pathway (not manually curated)
SREBF and miR33 in cholesterol and lipid homeostasis, organism-specific biosystem (from WikiPathways)
SREBF and miR33 in cholesterol and lipid homeostasis, organism-specific biosystemThis pathway describes transcription factor-microRNA circuits governing cholesterol and lipid homeostasis. It is based on a seminar by Dr. Anders Näär.

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: 223 organisms have orthologs with human gene Sirt6
The Hierarchical Catalog of 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)	IMP Inferred from Mutant Phenotype more info	PubMed
NAD-dependent histone deacetylase activity (H3-K9 specific)	ISO Inferred from Sequence Orthology more info
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
hydrolase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein deacetylase activity	ISO Inferred from Sequence Orthology more info
transcription corepressor activity	IGI Inferred from Genetic Interaction more info	PubMed

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
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, 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 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 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 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
cytoplasm	ISO Inferred from Sequence Orthology more info
nuclear telomeric heterochromatin	ISO Inferred from Sequence Orthology more info
nucleoplasm	ISO Inferred from Sequence Orthology more info
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 2.4.2.31

NP_853617.1

EC 2.4.2.31

XP_006513924.1

EC 2.4.2.31

XP_006513926.1

EC 2.4.2.31

XP_011241809.1

EC 2.4.2.31

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_001163430.1 → 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.

Source sequence(s)

AC153919, AK145929, BY606083, CJ302020

Consensus CDS

CCDS48645.1

UniProtKB/TrEMBL

Q3UKP1

Related

ENSMUSP00000113953.1, OTTMUSP00000039549, ENSMUST00000119324.7, OTTMUST00000075441

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_181586.3 → 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) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC153919, AK013316, BC052763, BY606083

Consensus CDS

CCDS24066.1

UniProtKB/Swiss-Prot

P59941

Related

ENSMUSP00000048971.8, OTTMUSP00000039548, ENSMUST00000042923.8, OTTMUST00000075440

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 ...

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 106

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

Reference GRCm38.p4 C57BL/6J

Genomic

NC_000076.6 Reference GRCm38.p4 C57BL/6J

Range

81621786..81627797 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006513861.3 → XP_006513924.1 NAD-dependent protein deacetylase sirtuin-6 isoform X1

Conserved Domains (1) summary

cd01410
Location:101 → 313

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 ...
XM_006513863.3 → XP_006513926.1 NAD-dependent protein deacetylase sirtuin-6 isoform X3

Conserved Domains (1) summary

cl00195
Location:1 → 185

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+, ...
XM_011243507.2 → 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+, ...