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+-protein-arginine ADP-ribosyltransferase activity; TORC2 complex binding activity; and histone deacetylase activity, NAD-dependent. Involved in several processes, including chromatin remodeling; regulation of nucleobase-containing compound metabolic process; and regulation of protein localization. Located in nucleus. Is active in chromatin. 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, Dec 2024]
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:

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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 ameliorates high glucose-induced podocyte cytoskeleton remodeling via the PI3K/AKT signaling pathway.
Title: Sirt6 ameliorates high glucose-induced podocyte cytoskeleton remodeling via the PI3K/AKT signaling pathway.
Sirtuin 6 inhibits group 3 innate lymphoid cell function and gut immunity by suppressing IL-22 production.
Title: Sirtuin 6 inhibits group 3 innate lymphoid cell function and gut immunity by suppressing IL-22 production.
Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.
Title: Sirt6 protects retinal ganglion cells and optic nerve from degeneration during aging and glaucoma.
Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis.
Title: Sirtuin 6 Deacetylates Apoptosis-Associated Speck-Like Protein (ASC) to Inhibit Endothelial Cell Pyroptosis in Atherosclerosis.
Impaired SUMOylation of FoxA1 promotes nonalcoholic fatty liver disease through down-regulation of Sirt6.
Title: Impaired SUMOylation of FoxA1 promotes nonalcoholic fatty liver disease through down-regulation of Sirt6.
SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.
Title: SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.
Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice.
Title: Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice.
Follistatin-like 1 protects against doxorubicin-induced cardiotoxicity by preventing mitochondrial dysfunction through the SIRT6/Nrf2 signaling pathway.
Title: Follistatin-like 1 protects against doxorubicin-induced cardiotoxicity by preventing mitochondrial dysfunction through the SIRT6/Nrf2 signaling pathway.
Sirtuin 6 ameliorates bleomycin-induced pulmonary fibrosis via activation of lipid catabolism.
Title: Sirtuin 6 ameliorates bleomycin-induced pulmonary fibrosis via activation of lipid catabolism.
SIRT6-mediated vascular smooth muscle cells senescence participates in the pathogenesis of abdominal aortic aneurysm.
Title: SIRT6-mediated vascular smooth muscle cells senescence participates in the pathogenesis of abdominal aortic aneurysm.

Submit: New GeneRIF Correction See all GeneRIFs (202)

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 damage sensor activity	ISO Inferred from Sequence Orthology more info
enables DNA damage sensor activity	ISS Inferred from Sequence or Structural Similarity more info
enables NAD+ binding	IBA Inferred from Biological aspect of Ancestor more info
enables NAD+ binding	ISS Inferred from Sequence or Structural Similarity 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+-protein-lysine ADP-ribosyltransferase activity	IEA Inferred from Electronic Annotation more info
enables NAD-dependent protein demyristoylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein demyristoylase activity	ISS Inferred from Sequence or Structural Similarity more info
enables NAD-dependent protein depalmitoylase activity	ISO Inferred from Sequence Orthology more info
enables NAD-dependent protein depalmitoylase activity	ISS Inferred from Sequence or Structural Similarity 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 TORC2 complex binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin DNA binding	ISO Inferred from Sequence Orthology more info
enables chromatin DNA binding	ISS Inferred from Sequence or Structural Similarity 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 damaged DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables histone H3K14 deacetylase activity, NAD-dependent	IEA Inferred from Electronic Annotation more info
enables histone H3K18 deacetylase activity, NAD-dependent	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K18 deacetylase activity, NAD-dependent	ISO Inferred from Sequence Orthology more info
enables histone H3K4 deacetylase activity, NAD-dependent	IEA Inferred from Electronic Annotation more info
enables histone H3K56 deacetylase activity, NAD-dependent	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K56 deacetylase activity, NAD-dependent	ISO Inferred from Sequence Orthology more info
enables histone H3K9 deacetylase activity, NAD-dependent	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K9 deacetylase activity, NAD-dependent	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K9 deacetylase activity, NAD-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K9 deacetylase activity, NAD-dependent	ISO Inferred from Sequence Orthology more info
enables histone H3K9 deacetylase activity, NAD-dependent	ISS Inferred from Sequence or Structural Similarity more info
enables histone H3K9 deacetylase activity, NAD-dependent	TAS Traceable Author Statement more info
enables histone H4K16 deacetylase activity, NAD-dependent	IEA Inferred from Electronic Annotation more info
enables histone deacetylase activity, NAD-dependent	ISO Inferred from Sequence Orthology more info
enables histone deacetylase activity, NAD-dependent	ISS Inferred from Sequence or Structural Similarity more info
enables lncRNA binding	IEA Inferred from Electronic Annotation more info
enables lncRNA binding	ISO Inferred from Sequence Orthology more info
enables nucleosome binding	ISO Inferred from Sequence Orthology more info
enables nucleosome binding	ISS Inferred from Sequence or Structural Similarity 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 homodimerization activity	ISS Inferred from Sequence or Structural Similarity 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 zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
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
involved_in cellular response to angiotensin	IEA Inferred from Electronic Annotation more info
involved_in cellular response to endothelin	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	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 double-strand break repair	ISS Inferred from Sequence or Structural Similarity 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
involved_in negative regulation of D-glucose import	IMP Inferred from Mutant Phenotype more info	PubMed
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	IEA Inferred from Electronic Annotation more info
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 gluconeogenesis	ISS Inferred from Sequence or Structural Similarity more info
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 glycolytic process	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
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 pericentric heterochromatin formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of blood vessel branching	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of blood vessel branching	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chondrocyte proliferation	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of telomere maintenance	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular endothelial cell proliferation	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
involved_in post-embryonic cardiac muscle cell growth involved in heart morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in post-translational protein modification	IEA Inferred from Electronic Annotation 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 delipidation	ISS Inferred from Sequence or Structural Similarity 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 destabilization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in protein localization to site of double-strand break	IEA Inferred from Electronic Annotation 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 double-strand break repair via homologous recombination	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
involved_in response to UV	ISO Inferred from Sequence Orthology more info
involved_in response to nutrient levels	IEA Inferred from Electronic Annotation more info
involved_in subtelomeric heterochromatin formation	IEA Inferred from Electronic Annotation more info
involved_in subtelomeric heterochromatin formation	ISO Inferred from Sequence Orthology more info
involved_in transposable element silencing	IDA Inferred from Direct Assay more info	PubMed
involved_in transposable element silencing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	ISO Inferred from Sequence Orthology more info
located_in chromatin	ISS Inferred from Sequence or Structural Similarity more info
located_in chromosome, subtelomeric region	ISS Inferred from Sequence or Structural Similarity more info
is_active_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
is_active_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
NOT located_in nucleolus	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISS Inferred from Sequence or Structural Similarity 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
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in pericentric heterochromatin	IEA Inferred from Electronic Annotation 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
located_in site of double-strand break	IEA Inferred from Electronic Annotation 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+, ...