SIRT6 sirtuin 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SIRT6provided by HGNC
Official Full Name: sirtuin 6provided by HGNC
Primary source: HGNC:HGNC:14934
See related: Ensembl:ENSG00000077463 MIM:606211; AllianceGenome:HGNC:14934
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SIR2L6; hSIRT6
Summary: This gene encodes a member of the sirtuin family of NAD-dependent enzymes that are implicated in cellular stress resistance, genomic stability, aging and energy homeostasis. The encoded protein is localized to the nucleus, exhibits ADP-ribosyl transferase and histone deacetylase activities, and plays a role in DNA repair, maintenance of telomeric chromatin, inflammation, lipid and glucose metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]
Expression: Ubiquitous expression in colon (RPKM 11.3), spleen (RPKM 5.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (4174109..4182563, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (4157416..4165866, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (4174106..4182560, complement)

Chromosome 19 - NC_000019.10 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

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.
Dynamic changes and clinical value of Sirt6 in acute coronary syndrome (ACS) patients.
Title: Dynamic changes and clinical value of Sirt6 in acute coronary syndrome (ACS) patients.
Binding to nucleosome poises human SIRT6 for histone H3 deacetylation.
Title: Binding to nucleosome poises human SIRT6 for histone H3 deacetylation.
Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy.
Title: Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy.
Ubiquitin-specific peptidase 10 attenuates the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6.
Title: Ubiquitin-specific peptidase 10 attenuates the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6.
SIRT6 Protects Against Lipopolysaccharide-Induced Inflammation in Human Pulmonary Lung Microvascular Endothelial Cells.
Title: SIRT6 Protects Against Lipopolysaccharide-Induced Inflammation in Human Pulmonary Lung Microvascular Endothelial Cells.
IL-38 alleviates atherogenic responses via SIRT6/HO-1 signaling: A promising strategy against obesity-related atherosclerosis.
Title: IL-38 alleviates atherogenic responses via SIRT6/HO-1 signaling: A promising strategy against obesity-related atherosclerosis.
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.
CTRP4 ameliorates inflammation, thereby attenuating the interaction between HUVECs and THP-1 monocytes through SIRT6/Nrf2 signaling.
Title: CTRP4 ameliorates inflammation, thereby attenuating the interaction between HUVECs and THP-1 monocytes through SIRT6/Nrf2 signaling.

Submit: New GeneRIF Correction See all GeneRIFs (295)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93156 (e-PCR)
- UniSTS:83753

SIRT6_244 (e-PCR)
- UniSTS:277713

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA damage sensor activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+ ADP-ribosyltransferase activity	TAS Traceable Author Statement more info	PubMed
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-lysine ADP-ribosyltransferase activity	IEA Inferred from Electronic Annotation more info
enables NAD+-protein ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein ADP-ribosyltransferase activity	TAS Traceable Author Statement more info	PubMed
enables NAD+-protein-arginine ADP-ribosyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables NAD-dependent histone H3K18 deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent histone H3K56 deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
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 deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent histone deacetylase activity	ISS Inferred from Sequence or Structural Similarity more info
enables NAD-dependent protein demyristoylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent protein depalmitoylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent protein depalmitoylase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NAD-dependent protein lysine deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD-dependent protein lysine deacetylase activity	TAS Traceable Author Statement more info
enables TORC2 complex binding	ISS Inferred from Sequence or Structural Similarity more info
enables chromatin DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables damaged DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables nucleosome binding	IDA Inferred from Direct Assay more info	PubMed
enables nucleotidyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in DNA repair-dependent chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in base-excision repair	IEA Inferred from Electronic Annotation more info
involved_in cardiac muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin remodeling	IDA Inferred from Direct Assay more info	PubMed
involved_in circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
involved_in glucose homeostasis	IEA Inferred from Electronic Annotation more info
involved_in ketone biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cellular senescence	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cellular senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression, epigenetic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gluconeogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of glucose import	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glycolytic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein import into nucleus	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription elongation by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in pericentric heterochromatin formation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of blood vessel branching	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chondrocyte proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity 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 fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype 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 localization to chromatin	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of stem cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of stem cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of stem cell population maintenance	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of stem cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vascular endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
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 delipidation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein destabilization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to site of double-strand break	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of lipid catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of lipid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in response to UV	IDA Inferred from Direct Assay more info	PubMed
involved_in retrotransposon silencing	ISS Inferred from Sequence or Structural Similarity more info
involved_in subtelomeric heterochromatin formation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome, subtelomeric region	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
NOT located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
part_of pericentric heterochromatin	IDA Inferred from Direct Assay more info	PubMed
is_active_in site of DNA damage	IDA Inferred from Direct Assay more info	PubMed
is_active_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: NAD-dependent protein deacylase sirtuin-6

Names: NAD-dependent protein deacetylase sirtuin-6; SIR2-like protein 6; protein mono-ADP-ribosyltransferase sirtuin-6; regulatory protein SIR2 homolog 6; sir2-related protein type 6; sirtuin type 6

NP_001180214.1

EC 2.3.1.286

NP_001307987.1

EC 2.3.1.286

NP_001307988.1

EC 2.3.1.286

NP_001307989.1

EC 2.3.1.286

NP_001307990.1

EC 2.3.1.286

NP_001307991.1

EC 2.3.1.286

NP_001307992.1

EC 2.3.1.286

NP_001307993.1

EC 2.3.1.286

NP_057623.2

EC 2.3.1.286

XP_024307307.1

EC 2.3.1.286

XP_054177165.1

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.

Genomic

NG_047153.1 RefSeqGene

Range

5037..13491

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193285.3 → NP_001180214.1 NAD-dependent protein deacylase sirtuin-6 isoform 2

Status: REVIEWED

Source sequence(s)

AC006930, AC016586, BC028220, CN364177

Consensus CDS

CCDS54199.1

UniProtKB/Swiss-Prot

Q8N6T7

Related

ENSP00000305310.5, ENST00000305232.10

Conserved Domains (1) summary

cl00195
Location:45 → 230

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+, ...
NM_001321058.2 → NP_001307987.1 NAD-dependent protein deacylase sirtuin-6 isoform 3

Status: REVIEWED

Source sequence(s)

AC016586, AK293348, BC028220

UniProtKB/TrEMBL

B4DDV3, M0QZ09

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+, ...
NM_001321059.2 → NP_001307988.1 NAD-dependent protein deacylase sirtuin-6 isoform 4

Status: REVIEWED

Source sequence(s)

AC006930, AK225567, BC028220, BQ060703, CN364177

UniProtKB/TrEMBL

M0QZ09

Related

ENSP00000470215.1, ENST00000597896.5

Conserved Domains (1) summary

cl00195
Location:45 → 196

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+, ...
NM_001321060.2 → NP_001307989.1 NAD-dependent protein deacylase sirtuin-6 isoform 5

Status: REVIEWED

Source sequence(s)

AC006930, AK225567, BC028220, CN364175, CN364177

UniProtKB/Swiss-Prot

Q8N6T7

Conserved Domains (1) summary

cl00195
Location:45 → 205

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+, ...
NM_001321061.2 → NP_001307990.1 NAD-dependent protein deacylase sirtuin-6 isoform 6

Status: REVIEWED

Source sequence(s)

AC016586, BC004218, BC028220, CN364177

UniProtKB/Swiss-Prot

Q8N6T7

Conserved Domains (1) summary

cl00195
Location:1 → 158

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+, ...
NM_001321062.2 → NP_001307991.1 NAD-dependent protein deacylase sirtuin-6 isoform 7

Status: REVIEWED

Source sequence(s)

AC006930, AK225567, BC028220, BP418952, CN364177

UniProtKB/Swiss-Prot

Q8N6T7

Conserved Domains (1) summary

cl00195
Location:1 → 122

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+, ...
NM_001321063.2 → NP_001307992.1 NAD-dependent protein deacylase sirtuin-6 isoform 8

Status: REVIEWED

Source sequence(s)

AC006930, AK225567, BC028220, BE281103, CN364177

Consensus CDS

CCDS82276.1

UniProtKB/TrEMBL

M0QXA0

Related

ENSP00000469001.1, ENST00000601488.5

Conserved Domains (1) summary

cl00195
Location:45 → 144

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+, ...
NM_001321064.2 → NP_001307993.1 NAD-dependent protein deacylase sirtuin-6 isoform 9

Status: REVIEWED

Source sequence(s)

AC006930, AK074810, AL559383, BC028220

Consensus CDS

CCDS82275.1

UniProtKB/TrEMBL

M0R1N9

Related

ENSP00000472023.1, ENST00000594279.5

Conserved Domains (1) summary

cl00195
Location:1 → 133

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+, ...
NM_016539.4 → NP_057623.2 NAD-dependent protein deacylase sirtuin-6 isoform 1

See identical proteins and their annotated locations for NP_057623.2

Status: REVIEWED

Source sequence(s)

AK074810, BC005026, CN364177

Consensus CDS

CCDS12122.1

UniProtKB/Swiss-Prot

B2RCD0, O75291, Q6IAF5, Q6PK99, Q8N6T7, Q8NCD2, Q9BSI5, Q9BWP3, Q9NRC7, Q9UQD1

Related

ENSP00000337332.1, ENST00000337491.7

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 ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

4174109..4182563 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024451539.2 → XP_024307307.1 NAD-dependent protein deacylase sirtuin-6 isoform X1

Conserved Domains (1) summary

cl00195
Location:42 → 233

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+, ...