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SIRT6 sirtuin 6 [ Homo sapiens (human) ]

Gene ID: 51548, updated on 4-Nov-2018

Summary

Official Symbol
SIRT6provided by HGNC
Official Full Name
sirtuin 6provided by HGNC
Primary source
HGNC:HGNC:14934
See related
Ensembl:ENSG00000077463 MIM:606211; Vega:OTTHUMG00000181847
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 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

Genomic context

See SIRT6 in Genome Data Viewer
Location:
19p13.3
Exon count:
9
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 19 NC_000019.10 (4174109..4182604, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (4174106..4182596, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene mitogen-activated protein kinase kinase 2 Neighboring gene cAMP responsive element binding protein 3 like 3 Neighboring gene ankyrin repeat domain 24 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Pathways from BioSystems

  • 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 biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • 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 biosystemHomology directed repair (HDR) of replication-independent DNA double strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM fol...
  • Homology Directed Repair, organism-specific biosystem (from REACTOME)
    Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
  • NAD+ biosynthetic pathways, organism-specific biosystem (from WikiPathways)
    NAD+ biosynthetic pathways, organism-specific biosystemNAD+ biosynthetic pathways. NAD+ levels are maintained by three independent pathways. First, the Preiss-Handler pathway uses dietary nicotinic acid and the enzyme nicotinic acid phosphoribosyltransfe...
  • NAD+ metabolism, organism-specific biosystem (from WikiPathways)
    NAD+ metabolism, organism-specific biosystemNAD+ metabolism in different cellular compartments. The different precursors to intracellular NAD metabolism - tryptophan, nicotinic acid (NA), nicotinamide, NR, and NMN - are shown, along with their...
  • Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
    Processing of DNA double-strand break ends, organism-specific biosystemHomology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ci...
  • 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.
  • Signaling events mediated by HDAC Class I, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by HDAC Class I, organism-specific biosystem
    Signaling events mediated by HDAC Class I

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

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 
NAD-dependent protein deacetylase activity TAS
Traceable Author Statement
more info
 
chromatin binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription corepressor activity IEA
Inferred from Electronic Annotation
more info
 
zinc ion binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
base-excision repair IEA
Inferred from Electronic Annotation
more info
 
glucose homeostasis IEA
Inferred from Electronic Annotation
more info
 
histone H3-K9 deacetylation IEA
Inferred from Electronic Annotation
more info
 
histone H3-K9 modification IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of glucose import IEA
Inferred from Electronic Annotation
more info
 
negative regulation of glycolytic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
positive regulation blood vessel branching IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of chondrocyte proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of chromatin silencing at telomere IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of fibroblast proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of stem cell proliferation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of telomere maintenance IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of telomeric heterochromatin assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of vascular endothelial cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
post-embryonic cardiac muscle cell growth involved in heart morphogenesis IEA
Inferred from Electronic Annotation
more info
 
protein ADP-ribosylation ISS
Inferred from Sequence or Structural Similarity
more info
 
protein ADP-ribosylation TAS
Traceable Author Statement
more info
PubMed 
protein destabilization IEA
Inferred from Electronic Annotation
more info
 
regulation of double-strand break repair via homologous recombination IDA
Inferred from Direct Assay
more info
PubMed 
response to nutrient levels IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IEA
Inferred from Electronic Annotation
more info
 
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 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus 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 protein deacetylase sirtuin-6
Names
SIR2-like protein 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_024307308.1

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.

Genomic

  1. NG_047153.1 RefSeqGene

    Range
    4996..13491
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001193285.2NP_001180214.1  NAD-dependent protein deacetylase sirtuin-6 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC006930, AC016586, BC028220, CN364177
    Consensus CDS
    CCDS54199.1
    UniProtKB/Swiss-Prot
    Q8N6T7
    Related
    ENSP00000305310.5, OTTHUMP00000267649, ENST00000305232.10, OTTHUMT00000457930
    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_001321058.1NP_001307987.1  NAD-dependent protein deacetylase sirtuin-6 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC016586, AK293348, BC028220, CN364177
    UniProtKB/Swiss-Prot
    Q8N6T7
    UniProtKB/TrEMBL
    B4DDV3
    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_001321059.1NP_001307988.1  NAD-dependent protein deacetylase sirtuin-6 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC006930, AK225567, BC028220, BQ060703, CN364177
    UniProtKB/Swiss-Prot
    Q8N6T7
    Related
    ENSP00000470215.1, OTTHUMP00000267696, ENST00000597896.5, OTTHUMT00000457997
    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_001321060.1NP_001307989.1  NAD-dependent protein deacetylase 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_001321061.1NP_001307990.1  NAD-dependent protein deacetylase 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_001321062.1NP_001307991.1  NAD-dependent protein deacetylase 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_001321063.1NP_001307992.1  NAD-dependent protein deacetylase sirtuin-6 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC006930, AK225567, BC028220, BE281103, CN364177
    Consensus CDS
    CCDS82276.1
    UniProtKB/Swiss-Prot
    Q8N6T7
    UniProtKB/TrEMBL
    M0QXA0
    Related
    ENSP00000469001.1, OTTHUMP00000267648, ENST00000601488.5, OTTHUMT00000457929
    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_001321064.1NP_001307993.1  NAD-dependent protein deacetylase sirtuin-6 isoform 9

    Status: REVIEWED

    Source sequence(s)
    AC006930, AK074810, AL559383, BC028220
    Consensus CDS
    CCDS82275.1
    UniProtKB/Swiss-Prot
    Q8N6T7
    UniProtKB/TrEMBL
    M0R1N9
    Related
    ENSP00000472023.1, OTTHUMP00000267651, ENST00000594279.5, OTTHUMT00000457935
    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_016539.3NP_057623.2  NAD-dependent protein deacetylase 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
    Q8N6T7
    Related
    ENSP00000337332.1, OTTHUMP00000267650, ENST00000337491.6, OTTHUMT00000457931
    Conserved Domains (1) summary
    cd01410
    Location:45257
    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: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p12 Primary Assembly

    Range
    4174109..4182604 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024451540.1XP_024307308.1  NAD-dependent protein deacetylase sirtuin-6 isoform X2

    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+, ...
  2. XM_024451539.1XP_024307307.1  NAD-dependent protein deacetylase 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+, ...
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