Human Gene SIRT6 (ENST00000337491.7) from GENCODE V44
  Description: Homo sapiens sirtuin 6 (SIRT6), transcript variant 1, mRNA. (from RefSeq NM_016539)
RefSeq Summary (NM_016539): 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].
Gencode Transcript: ENST00000337491.7
Gencode Gene: ENSG00000077463.15
Transcript (Including UTRs)
   Position: hg38 chr19:4,174,109-4,182,563 Size: 8,455 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg38 chr19:4,174,617-4,182,539 Size: 7,923 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:4,174,109-4,182,563)mRNA (may differ from genome)Protein (355 aa)
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OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: SIR6_HUMAN
DESCRIPTION: RecName: Full=NAD-dependent protein deacetylase sirtuin-6; EC=3.5.1.-; AltName: Full=Regulatory protein SIR2 homolog 6; AltName: Full=SIR2-like protein 6;
FUNCTION: NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF- kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.
CATALYTIC ACTIVITY: NAD(+) + an acetylprotein = nicotinamide + O- acetyl-ADP-ribose + a protein.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBUNIT: Interacts with RELA. Interacts with RBBP8; the interaction deacetylates RBBP8.
INTERACTION: Q04206:RELA; NbExp=4; IntAct=EBI-712415, EBI-73886;
SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Note=Predominantly nuclear. Associated with telomeric heterochromatin regions.
MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins is likely some inefficient side reaction of the deacetylase activity and may not be physiologically relevant (By similarity).
SIMILARITY: Belongs to the sirtuin family. Class IV subfamily.
SIMILARITY: Contains 1 deacetylase sirtuin-type domain.
SEQUENCE CAUTION: Sequence=AAC34468.1; Type=Erroneous gene model prediction; Sequence=AAD15478.1; Type=Erroneous gene model prediction; Sequence=AAH04218.1; Type=Erroneous translation; Note=Wrong choice of CCDS;

-  Primer design for this transcript
 

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-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 21.77 RPKM in Colon - Transverse
Total median expression: 421.52 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -6.1024-0.254 Picture PostScript Text
3' UTR -214.60508-0.422 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003000 - Sirtuin
IPR026590 - Ssirtuin_cat_dom

Pfam Domains:
PF02146 - Sir2 family

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3K35 - X-ray MuPIT 3PKI - X-ray MuPIT 3PKJ - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q8N6T7
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsemblWormBase 
Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence 
AlignmentAlignmentAlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003682 chromatin binding
GO:0003714 transcription corepressor activity
GO:0003950 NAD+ ADP-ribosyltransferase activity
GO:0003956 NAD(P)+-protein-arginine ADP-ribosyltransferase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0017136 NAD-dependent histone deacetylase activity
GO:0033558 protein deacetylase activity
GO:0034979 NAD-dependent protein deacetylase activity
GO:0046872 metal ion binding
GO:0046969 NAD-dependent histone deacetylase activity (H3-K9 specific)
GO:0070403 NAD+ binding

Biological Process:
GO:0003247 post-embryonic cardiac muscle cell growth involved in heart morphogenesis
GO:0006284 base-excision repair
GO:0006471 protein ADP-ribosylation
GO:0006476 protein deacetylation
GO:0008285 negative regulation of cell proliferation
GO:0010569 regulation of double-strand break repair via homologous recombination
GO:0016575 histone deacetylation
GO:0031648 protein destabilization
GO:0031667 response to nutrient levels
GO:0031940 positive regulation of chromatin silencing at telomere
GO:0032206 positive regulation of telomere maintenance
GO:0042593 glucose homeostasis
GO:0045820 negative regulation of glycolytic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:0046325 negative regulation of glucose import
GO:0048146 positive regulation of fibroblast proliferation
GO:0061647 histone H3-K9 modification
GO:1902732 positive regulation of chondrocyte proliferation
GO:1905549 positive regulation of telomeric heterochromatin assembly
GO:1905555 positive regulation blood vessel branching
GO:1905564 positive regulation of vascular endothelial cell proliferation
GO:1990619 histone H3-K9 deacetylation
GO:2000648 positive regulation of stem cell proliferation

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005724 nuclear telomeric heterochromatin
GO:0005737 cytoplasm
GO:0005730 nucleolus


-  Descriptions from all associated GenBank mRNAs
  AL365375 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 1506345.
BC005026 - Homo sapiens sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae), mRNA (cDNA clone MGC:12574 IMAGE:2820472), complete cds.
BC004218 - Homo sapiens sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae), mRNA (cDNA clone MGC:4601 IMAGE:3352203), complete cds.
BC028220 - Homo sapiens sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae), mRNA (cDNA clone MGC:40041 IMAGE:5217599), complete cds.
AF233396 - Homo sapiens sir2-related protein type 6 (SIRT6) mRNA, complete cds.
LF384679 - JP 2014500723-A/192182: Polycomb-Associated Non-Coding RNAs.
MA620256 - JP 2018138019-A/192182: Polycomb-Associated Non-Coding RNAs.
AK293348 - Homo sapiens cDNA FLJ52470 complete cds, highly similar to Mono-ADP-ribosyltransferase sirtuin-6 (EC 2.4.2.31).
AK074810 - Homo sapiens cDNA FLJ90329 fis, clone NT2RP2001948, weakly similar to HST2 PROTEIN.
JD185622 - Sequence 166646 from Patent EP1572962.
JD292610 - Sequence 273634 from Patent EP1572962.
AK225567 - Homo sapiens mRNA for Mono-ADP-ribosyltransferase sirtuin-6 variant, clone: KDN07709.
JD251645 - Sequence 232669 from Patent EP1572962.
JD150343 - Sequence 131367 from Patent EP1572962.
JD504989 - Sequence 486013 from Patent EP1572962.
JD149576 - Sequence 130600 from Patent EP1572962.
JD387611 - Sequence 368635 from Patent EP1572962.
JD114760 - Sequence 95784 from Patent EP1572962.
JD390865 - Sequence 371889 from Patent EP1572962.
JD421119 - Sequence 402143 from Patent EP1572962.
JD278427 - Sequence 259451 from Patent EP1572962.
JD231737 - Sequence 212761 from Patent EP1572962.
JD157471 - Sequence 138495 from Patent EP1572962.
JD455592 - Sequence 436616 from Patent EP1572962.
JD235759 - Sequence 216783 from Patent EP1572962.
JD041866 - Sequence 22890 from Patent EP1572962.
JD196027 - Sequence 177051 from Patent EP1572962.
JD211523 - Sequence 192547 from Patent EP1572962.
JD076608 - Sequence 57632 from Patent EP1572962.
KJ902603 - Synthetic construct Homo sapiens clone ccsbBroadEn_11997 SIRT6 gene, encodes complete protein.
CU678868 - Synthetic construct Homo sapiens gateway clone IMAGE:100017080 5' read SIRT6 mRNA.
KJ893938 - Synthetic construct Homo sapiens clone ccsbBroadEn_03332 SIRT6 gene, encodes complete protein.
KJ906179 - Synthetic construct Homo sapiens clone ccsbBroadEn_15849 SIRT6 gene, encodes complete protein.
AK315048 - Homo sapiens cDNA, FLJ95996, highly similar to Homo sapiens sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae) (SIRT6), mRNA.
DQ896358 - Synthetic construct Homo sapiens clone IMAGE:100010818; FLH193610.01L; RZPDo839A0369D sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae) (SIRT6) gene, encodes complete protein.
EU176413 - Synthetic construct Homo sapiens clone IMAGE:100006505; FLH193617.01X; RZPDo839A07252D sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae) (SIRT6) gene, encodes complete protein.
AB528632 - Synthetic construct DNA, clone: pF1KB6478, Homo sapiens SIRT6 gene for sirtuin (silent mating type information regulation 2 homolog) 6, without stop codon, in Flexi system.
CR457200 - Homo sapiens full open reading frame cDNA clone RZPDo834B0613D for gene SIRT6, sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae); complete cds, incl. stopcodon.
AK299420 - Homo sapiens cDNA FLJ52735 complete cds, highly similar to Mono-ADP-ribosyltransferase sirtuin-6 (EC 2.4.2.31).
CU678618 - Synthetic construct Homo sapiens gateway clone IMAGE:100022390 5' read SIRT6 mRNA.
AK301247 - Homo sapiens cDNA FLJ60174 complete cds, moderately similar to Mono-ADP-ribosyltransferase sirtuin-6 (EC 2.4.2.31).
LF323191 - JP 2014500723-A/130694: Polycomb-Associated Non-Coding RNAs.
MA558768 - JP 2018138019-A/130694: Polycomb-Associated Non-Coding RNAs.
LF323192 - JP 2014500723-A/130695: Polycomb-Associated Non-Coding RNAs.
MA558769 - JP 2018138019-A/130695: Polycomb-Associated Non-Coding RNAs.
JD094597 - Sequence 75621 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q8N6T7 (Reactome details) participates in the following event(s):

R-HSA-5685953 SIRT6 deacetylates RBBP8
R-HSA-5693607 Processing of DNA double-strand break ends
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-5693538 Homology Directed Repair
R-HSA-5693532 DNA Double-Strand Break Repair
R-HSA-73894 DNA Repair

-  Other Names for This Gene
  Alternate Gene Symbols: B2RCD0, ENST00000337491.1, ENST00000337491.2, ENST00000337491.3, ENST00000337491.4, ENST00000337491.5, ENST00000337491.6, NM_016539, O75291, Q6IAF5, Q6PK99, Q8N6T7, Q8NCD2, Q9BSI5, Q9BWP3, Q9NRC7, Q9UQD1, SIR2L6, SIR6_HUMAN, uc002lzo.1, uc002lzo.2, uc002lzo.3, uc002lzo.4, uc002lzo.5
UCSC ID: ENST00000337491.7
RefSeq Accession: NM_016539
Protein: Q8N6T7 (aka SIR6_HUMAN)
CCDS: CCDS12122.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.