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SIRT6 sirtuin 6 [ Homo sapiens (human) ]

Gene ID: 51548, updated on 10-Dec-2024

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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

See SIRT6 in Genome Data Viewer
Location:
19p13.3
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (4174109..4182563, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (4157416..4165866, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (4174106..4182560, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:4089732-4090508 Neighboring gene mitogen-activated protein kinase kinase 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13757 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13758 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:4116105-4116291 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9881 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9882 Neighboring gene Sharpr-MPRA regulatory region 2607 Neighboring gene Sharpr-MPRA regulatory region 6873 Neighboring gene MPRA-validated peak3267 silencer Neighboring gene cAMP responsive element binding protein 3 like 3 Neighboring gene Sharpr-MPRA regulatory region 11650 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13759 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13760 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13761 Neighboring gene ankyrin repeat domain 24 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:4199326-4199972 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:4199973-4200619 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:4204935-4205148 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:4216177-4216676 Neighboring gene MPRA-validated peak3273 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13762 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:4230793-4231294 Neighboring gene Epstein-Barr virus induced 3

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables DNA damage sensor activity IDA
Inferred from Direct Assay
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 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 poly-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+-protein-lysine ADP-ribosyltransferase activity IEA
Inferred from Electronic Annotation
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 chromatin binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables damaged DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables enzyme regulator activity IDA
Inferred from Direct Assay
more info
PubMed 
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 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 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, hydrolytic mechanism EXP
Inferred from Experiment
more info
PubMed 
enables histone H4K16 deacetylase activity, NAD-dependent IEA
Inferred from Electronic Annotation
more info
 
enables histone deacetylase activity, NAD-dependent IDA
Inferred from Direct Assay
more info
PubMed 
enables histone deacetylase activity, NAD-dependent ISS
Inferred from Sequence or Structural Similarity
more info
 
enables histone deacetylase regulator activity IDA
Inferred from Direct Assay
more info
PubMed 
enables nucleosome binding IDA
Inferred from Direct Assay
more info
PubMed 
enables nucleosome binding IMP
Inferred from Mutant Phenotype
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 D-glucose import IEA
Inferred from Electronic Annotation
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 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 import into nucleus IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein import into nucleus 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 subtelomeric heterochromatin formation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in transposable element silencing ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
is_active_in chromatin IDA
Inferred from Direct Assay
more info
PubMed 
located_in 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
 
is_active_in 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

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
NP_001307987.1
NP_001307988.1
NP_001307989.1
NP_001307990.1
NP_001307991.1
NP_001307992.1
NP_001307993.1
NP_057623.2
XP_024307307.1
XP_054177165.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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

  1. NG_047153.1 RefSeqGene

    Range
    5037..13491
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001193285.3NP_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:45230
    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+, ...
  2. NM_001321058.2NP_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:1185
    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+, ...
  3. NM_001321059.2NP_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:45196
    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+, ...
  4. NM_001321060.2NP_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:45205
    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+, ...
  5. NM_001321061.2NP_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:1158
    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+, ...
  6. NM_001321062.2NP_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:1122
    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+, ...
  7. NM_001321063.2NP_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:45144
    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+, ...
  8. NM_001321064.2NP_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:1133
    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+, ...
  9. NM_016539.4NP_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:45257
    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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    4174109..4182563 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    Conserved Domains (1) summary
    cl00195
    Location:42233
    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+, ...

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    4157416..4165866 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321190.1XP_054177165.1  NAD-dependent protein deacylase sirtuin-6 isoform X1