SIRT6 sirtuin 6 [Homo sapiens] - Gene

Help top of page

Summary

Official Symbol: SIRT6provided by HGNC
Official Full Name: sirtuin 6provided by HGNC
Primary source: HGNC:14934
See related: Ensembl:ENSG00000077463; HPRD:12093; MIM:606211
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
Summary: This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

Help top of page

Genomic context

Location :: 19p13.3

Sequence :: Chromosome: 19; NC_000019.9 (4174106..4182596, complement)

See SIRT6 in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 Genomic Context describing neighboring genes

Help top of page

Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Help top of page

Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque
Title: Association of the sirtuin and mitochondrial uncoupling protein genes with carotid plaque.
SIRT6 knockdown in HDFs influence the synthesis and degradation of collagen by hyperactive NF-kappaB signalling, which leads to a decrease in dermal collagen fibrils. SIRT6 may therefore play an important role in the process of skin anti-aging.
Title: Effects of SIRT6 silencing on collagen metabolism in human dermal fibroblasts.
SIRT6 overexpression selectively kills cancer cells.
Title: SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells.
This study suggested that altered SIRT1, 2 and 6 expression is state-dependent and might be associated with the pathogenesis and/or pathophysiology of mood disorders.
Title: Altered sirtuin deacetylase gene expression in patients with a mood disorder.
SIRT6 is important for maintaining telomeric chromatin structure that is required for silencing of nearby genes.
Title: SIRT6 is required for maintenance of telomere position effect in human cells.
SIRT6 could act as an NAD(+) metabolite sensor
Title: Structure and biochemical functions of SIRT6.
results indicate that SIRT6 physically associates with PARP1 and mono-ADP-ribosylates PARP1 on lysine residue 521, stimulating PARP1 poly-ADP-ribosylase activity and enhancing DSB repair under oxidative stress
Title: SIRT6 promotes DNA repair under stress by activating PARP1.
These findings suggest that accelerated epithelial senescence plays a role in idiopathic pulmonary fibrosis pathogenesis through perpetuating abnormal epithelial-mesenchymal interactions, which can be antagonized by SIRT6.
Title: Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells.
identified double-strand break(DSB) resection protein CtIP as a SIRT6 interaction partner; showed SIRT6-dependent CtIP deacetylation promotes resection;CtIP identified as key substrate by which SIRT6 facilitates DSB processing and homologous recombination
Title: Human SIRT6 promotes DNA end resection through CtIP deacetylation.
SIRT6 associates dynamically with chromatin in response to DNA damage, and stabilizes the DNA double-strand break (DSB) repair factor, DNA-dependent protein kinase (DNA-PK), at DSBs.
Title: SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair.

Submit: New GeneRIF Correction See all (14)

Help top of page

Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Help top of page

Products	Interactant	Other Gene	Source	Pubs	Description
Q8N6T7	Q12873	CHD3	HPRD	PubMed
Q8N6T7	Q9UKW6	ELF5	HPRD	PubMed
Q8N6T7	P08670	VIM	HPRD	PubMed
BioGRID:119603	BioGRID:117117	CCNDBP1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:119603	BioGRID:107532	CHD3	BioGRID	PubMed	Two-hybrid
BioGRID:119603	BioGRID:108316	ELF5	BioGRID	PubMed	Two-hybrid
BioGRID:119603	BioGRID:116298	FAF1	BioGRID	PubMed	Two-hybrid
BioGRID:119603	BioGRID:114012	NR0B2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:119603	BioGRID:111577	PRKDC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-localization
BioGRID:119603	BioGRID:111902	RELA	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:119603	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:119603	BioGRID:113169	UBE2D1	BioGRID	PubMed	Two-hybrid
BioGRID:119603	BioGRID:113272	VIM	BioGRID	PubMed	Two-hybrid
BioGRID:119603	BioGRID:113353	XRCC5	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:119603	BioGRID:108822	XRCC6	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:119603	BioGRID:1205541	tat	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
NAD(P)+-protein-arginine ADP-ribosyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
NAD+ ADP-ribosyltransferase activity	TAS Traceable Author Statement more info	PubMed
NAD+ binding	ISS Inferred from Sequence or Structural Similarity more info
NAD-dependent histone deacetylase activity	ISS Inferred from Sequence or Structural Similarity more info
NAD-dependent histone deacetylase activity (H3-K9 specific)	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 binding	IPI Inferred from Physical Interaction more info	PubMed
zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
protein ADP-ribosylation	ISS Inferred from Sequence or Structural Similarity more info
protein ADP-ribosylation	TAS Traceable Author Statement more info	PubMed
protein deacetylation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
nuclear telomeric heterochromatin	IDA Inferred from Direct Assay more info	PubMed
NOT nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Preferred Names: NAD-dependent deacetylase sirtuin-6

Names: NAD-dependent deacetylase sirtuin-6; sirtuin type 6; SIR2-like protein 6; sir2-related protein type 6

NP_001180214.1

EC 2.4.2.31

NP_057623.2

EC 2.4.2.31

Help top of page

NCBI Reference Sequences (RefSeq)

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_001193285.1 → NP_001180214.1 NAD-dependent deacetylase sirtuin-6 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC006930, AC016586

Consensus CDS

CCDS54199.1

UniProtKB/Swiss-Prot

Q8N6T7

Related

ENSP00000305310, ENST00000305232

Conserved Domains (2) summary

PRK00481
Location:36 – 242
Blast Score: 379

PRK00481; NAD-dependent deacetylase; Provisional

cl00195
Location:45 – 230
Blast Score: 675

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_016539.2 → NP_057623.2 NAD-dependent deacetylase sirtuin-6 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AF233396, AK074810, BC005026

Consensus CDS

CCDS12122.1

UniProtKB/Swiss-Prot

Q8N6T7

Related

ENSP00000337332, ENST00000337491

Conserved Domains (2) summary

cd01410
Location:45 – 257
Blast Score: 767

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 ...

PRK00481
Location:36 – 269
Blast Score: 418

PRK00481; NAD-dependent deacetylase; Provisional

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000019.9 Reference GRCh37.p5 Primary Assembly

Range

4174106..4182596, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

3937486..3945942, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Help top of page

Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC005620.1	AAC34468.1
genomic	AC006930.1	AAD15478.1
genomic	AC016586.9 (199143..205641)	None
genomic	CH471139.2	EAW69251.1
		EAW69252.1
		EAW69253.1
		EAW69254.1
		EAW69255.1
		EAW69256.1
		EAW69257.1
		EAW69258.1
		EAW69259.1
genomic	CS330066.1	CAL00161.1
mRNA	AF233396.1	AAF43432.1
mRNA	AK074810.1	BAC11222.1
mRNA	AK225567.1	None
mRNA	AK293348.1	BAG56864.1
mRNA	AK299420.1	BAH13027.1
mRNA	AK301247.1	BAG62814.1
mRNA	AK315048.1	BAG37527.1
mRNA	BC004218.2	AAH04218.1
mRNA	BC005026.1	AAH05026.1
mRNA	BC028220.1	AAH28220.1
mRNA	CR457200.1	CAG33481.1
other-genetic	DQ896358.2	ABM87357.1
other-genetic	EU176413.1	ABW03864.1