UniProtKB - Q8N6T7 (SIR6_HUMAN)
Protein
NAD-dependent protein deacetylase sirtuin-6
Gene
SIRT6
Organism
Homo sapiens (Human)
Status
Functioni
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.By similarity5 Publications
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
Catalytic activityi
- H2O + N6-acetyl-L-lysyl-[protein] + NAD+ = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamidePROSITE-ProRule annotation1 PublicationEC:2.3.1.286PROSITE-ProRule annotation1 Publication
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 133 | Proton acceptor | 1 | |
Metal bindingi | 141 | ZincPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 144 | ZincPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 166 | ZincPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 177 | ZincPROSITE-ProRule annotation1 Publication | 1 | |
Binding sitei | 258 | NAD; via amide nitrogen | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 52 – 71 | NADAdd BLAST | 20 | |
Nucleotide bindingi | 113 – 116 | NAD | 4 | |
Nucleotide bindingi | 214 – 216 | NAD | 3 | |
Nucleotide bindingi | 240 – 242 | NAD | 3 |
GO - Molecular functioni
- chromatin binding Source: Ensembl
- deacetylase activity Source: GO_Central
- histone deacetylase activity Source: GO_Central
- NAD(P)+-protein-arginine ADP-ribosyltransferase activity Source: UniProtKB
- NAD+ ADP-ribosyltransferase activity Source: BHF-UCL
- NAD+ binding Source: UniProtKB
- NAD-dependent histone deacetylase activity Source: UniProtKB
- NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB
- NAD-dependent protein deacetylase activity Source: Reactome
- transcription corepressor activity Source: GO_Central
- zinc ion binding Source: UniProtKB
GO - Biological processi
- base-excision repair Source: Ensembl
- glucose homeostasis Source: Ensembl
- histone H3 deacetylation Source: GO_Central
- negative regulation of cell population proliferation Source: Ensembl
- negative regulation of glucose import Source: Ensembl
- negative regulation of glycolytic process Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: GO_Central
- positive regulation blood vessel branching Source: BHF-UCL
- positive regulation of chondrocyte proliferation Source: BHF-UCL
- positive regulation of chromatin silencing at telomere Source: BHF-UCL
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of fibroblast proliferation Source: Ensembl
- positive regulation of stem cell proliferation Source: Ensembl
- positive regulation of subtelomeric heterochromatin assembly Source: BHF-UCL
- positive regulation of telomere maintenance Source: BHF-UCL
- positive regulation of transcription factor catabolic process Source: CACAO
- positive regulation of vascular endothelial cell proliferation Source: BHF-UCL
- post-embryonic cardiac muscle cell growth involved in heart morphogenesis Source: Ensembl
- protein ADP-ribosylation Source: UniProtKB
- protein deacetylation Source: CACAO
- protein destabilization Source: Ensembl
- regulation of double-strand break repair via homologous recombination Source: UniProtKB
- response to nutrient levels Source: Ensembl
Keywordsi
Molecular function | Transferase |
Ligand | Metal-binding, NAD, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q8N6T7 |
Reactomei | R-HSA-1912408, Pre-NOTCH Transcription and Translation R-HSA-5693607, Processing of DNA double-strand break ends |
SIGNORi | Q8N6T7 |
Names & Taxonomyi
Protein namesi | Recommended name: NAD-dependent protein deacetylase sirtuin-6 (EC:2.3.1.286)Alternative name(s): Regulatory protein SIR2 homolog 6 SIR2-like protein 6 |
Gene namesi | Name:SIRT6 Synonyms:SIR2L6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000077463.14 |
HGNCi | HGNC:14934, SIRT6 |
MIMi | 606211, gene |
neXtProti | NX_Q8N6T7 |
Subcellular locationi
Nucleus
- nucleoplasm 3 Publications
Note: Predominantly nuclear. Associated with telomeric heterochromatin regions.
Nucleus
- nucleoplasm Source: UniProtKB
- nucleus Source: BHF-UCL
Other locations
- chromosome, subtelomeric region Source: GO_Central
- cytoplasm Source: Ensembl
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 133 | H → Y: Loss of enzyme activity. Abolishes RBBP8 deacetylation and promotion of DNA end resection after DNA damage. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 51548 |
OpenTargetsi | ENSG00000077463 |
Orphaneti | 580933, Lethal brain and heart developmental defects |
PharmGKBi | PA37939 |
Miscellaneous databases
Pharosi | Q8N6T7, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2163182 |
GuidetoPHARMACOLOGYi | 2712 |
Polymorphism and mutation databases
BioMutai | SIRT6 |
DMDMi | 38258612 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000110269 | 2 – 355 | NAD-dependent protein deacetylase sirtuin-6Add BLAST | 354 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineCombined sources | 1 | |
Modified residuei | 10 | PhosphoserineCombined sources | 1 | |
Modified residuei | 294 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 303 | PhosphoserineCombined sources | 1 | |
Modified residuei | 330 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q8N6T7 |
jPOSTi | Q8N6T7 |
MassIVEi | Q8N6T7 |
MaxQBi | Q8N6T7 |
PaxDbi | Q8N6T7 |
PeptideAtlasi | Q8N6T7 |
PRIDEi | Q8N6T7 |
ProteomicsDBi | 72232 [Q8N6T7-1] 72233 [Q8N6T7-2] |
PTM databases
iPTMneti | Q8N6T7 |
PhosphoSitePlusi | Q8N6T7 |
Expressioni
Gene expression databases
Bgeei | ENSG00000077463, Expressed in mucosa of transverse colon and 180 other tissues |
ExpressionAtlasi | Q8N6T7, baseline and differential |
Genevisiblei | Q8N6T7, HS |
Organism-specific databases
HPAi | ENSG00000077463, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with RELA.
Interacts with RBBP8; the interaction deacetylates RBBP8.
3 PublicationsBinary interactionsi
Hide detailsProtein-protein interaction databases
BioGRIDi | 119603, 204 interactors |
DIPi | DIP-47346N |
IntActi | Q8N6T7, 71 interactors |
MINTi | Q8N6T7 |
STRINGi | 9606.ENSP00000337332 |
Chemistry databases
BindingDBi | Q8N6T7 |
Miscellaneous databases
RNActi | Q8N6T7, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q8N6T7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q8N6T7 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 35 – 274 | Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST | 240 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 287 – 345 | Pro-richAdd BLAST | 59 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1905, Eukaryota |
GeneTreei | ENSGT00940000160088 |
HOGENOMi | CLU_023643_6_0_1 |
InParanoidi | Q8N6T7 |
OMAi | NVLDWEH |
OrthoDBi | 1503290at2759 |
PhylomeDBi | Q8N6T7 |
TreeFami | TF106184 |
Family and domain databases
IDEALi | IID00486 |
InterProi | View protein in InterPro IPR029035, DHS-like_NAD/FAD-binding_dom IPR003000, Sirtuin IPR026590, Ssirtuin_cat_dom |
Pfami | View protein in Pfam PF02146, SIR2, 2 hits |
SUPFAMi | SSF52467, SSF52467, 1 hit |
PROSITEi | View protein in PROSITE PS50305, SIRTUIN, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8N6T7-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSVNYAAGLS PYADKGKCGL PEIFDPPEEL ERKVWELARL VWQSSSVVFH
60 70 80 90 100
TGAGISTASG IPDFRGPHGV WTMEERGLAP KFDTTFESAR PTQTHMALVQ
110 120 130 140 150
LERVGLLRFL VSQNVDGLHV RSGFPRDKLA ELHGNMFVEE CAKCKTQYVR
160 170 180 190 200
DTVVGTMGLK ATGRLCTVAK ARGLRACRGE LRDTILDWED SLPDRDLALA
210 220 230 240 250
DEASRNADLS ITLGTSLQIR PSGNLPLATK RRGGRLVIVN LQPTKHDRHA
260 270 280 290 300
DLRIHGYVDE VMTRLMKHLG LEIPAWDGPR VLERALPPLP RPPTPKLEPK
310 320 330 340 350
EESPTRINGS IPAGPKQEPC AQHNGSEPAS PKRERPTSPA PHRPPKRVKA
KAVPS
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0QZ09 | M0QZ09_HUMAN | NAD-dependent protein deacetylase s... | SIRT6 | 275 | Annotation score: | ||
M0R1N9 | M0R1N9_HUMAN | NAD-dependent protein deacetylase s... | SIRT6 hCG_2004101 | 176 | Annotation score: | ||
M0R1F6 | M0R1F6_HUMAN | NAD-dependent protein deacetylase s... | SIRT6 | 186 | Annotation score: | ||
M0QXA0 | M0QXA0_HUMAN | NAD-dependent protein deacetylase s... | SIRT6 | 187 | Annotation score: | ||
M0R0B2 | M0R0B2_HUMAN | NAD-dependent protein deacetylase s... | SIRT6 | 43 | Annotation score: |
Sequence cautioni
The sequence AAC34468 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAD15478 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAH04218 differs from that shown. Reason: Erroneous translation. Wrong choice of CCDS.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 42 | W → R in CAG33481 (Ref. 3) Curated | 1 | |
Sequence conflicti | 249 | H → Y in AAH04218 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 267 | K → E in AAF43432 (PubMed:10873683).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_017154 | 46 | S → N3 PublicationsCorresponds to variant dbSNP:rs352493Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_008733 | 179 – 205 | Missing in isoform 2. 1 PublicationAdd BLAST | 27 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF233396 mRNA Translation: AAF43432.1 AK074810 mRNA Translation: BAC11222.1 AK315048 mRNA Translation: BAG37527.1 CR457200 mRNA Translation: CAG33481.1 AC005620 Genomic DNA Translation: AAC34468.1 Sequence problems. AC006930 Genomic DNA Translation: AAD15478.1 Sequence problems. CH471139 Genomic DNA Translation: EAW69252.1 BC004218 mRNA Translation: AAH04218.1 Sequence problems. BC005026 mRNA Translation: AAH05026.1 BC028220 mRNA Translation: AAH28220.1 |
CCDSi | CCDS12122.1 [Q8N6T7-1] CCDS54199.1 [Q8N6T7-2] |
RefSeqi | NP_001180214.1, NM_001193285.2 [Q8N6T7-2] NP_001307987.1, NM_001321058.1 NP_001307988.1, NM_001321059.1 NP_001307989.1, NM_001321060.1 NP_001307990.1, NM_001321061.1 NP_001307991.1, NM_001321062.1 NP_001307992.1, NM_001321063.1 NP_001307993.1, NM_001321064.1 NP_057623.2, NM_016539.3 [Q8N6T7-1] |
Genome annotation databases
Ensembli | ENST00000305232; ENSP00000305310; ENSG00000077463 [Q8N6T7-2] ENST00000337491; ENSP00000337332; ENSG00000077463 [Q8N6T7-1] |
GeneIDi | 51548 |
KEGGi | hsa:51548 |
UCSCi | uc002lzo.4, human [Q8N6T7-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF233396 mRNA Translation: AAF43432.1 AK074810 mRNA Translation: BAC11222.1 AK315048 mRNA Translation: BAG37527.1 CR457200 mRNA Translation: CAG33481.1 AC005620 Genomic DNA Translation: AAC34468.1 Sequence problems. AC006930 Genomic DNA Translation: AAD15478.1 Sequence problems. CH471139 Genomic DNA Translation: EAW69252.1 BC004218 mRNA Translation: AAH04218.1 Sequence problems. BC005026 mRNA Translation: AAH05026.1 BC028220 mRNA Translation: AAH28220.1 |
CCDSi | CCDS12122.1 [Q8N6T7-1] CCDS54199.1 [Q8N6T7-2] |
RefSeqi | NP_001180214.1, NM_001193285.2 [Q8N6T7-2] NP_001307987.1, NM_001321058.1 NP_001307988.1, NM_001321059.1 NP_001307989.1, NM_001321060.1 NP_001307990.1, NM_001321061.1 NP_001307991.1, NM_001321062.1 NP_001307992.1, NM_001321063.1 NP_001307993.1, NM_001321064.1 NP_057623.2, NM_016539.3 [Q8N6T7-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3K35 | X-ray | 2.00 | A/B/C/D/E/F | 3-318 | [»] | |
3PKI | X-ray | 2.04 | A/B/C/D/E/F | 2-355 | [»] | |
3PKJ | X-ray | 2.12 | A/B/C/D/E/F | 2-355 | [»] | |
3ZG6 | X-ray | 2.20 | A | 1-296 | [»] | |
5MF6 | X-ray | 1.87 | A/B | 13-308 | [»] | |
5MFP | X-ray | 1.98 | A/B | 13-308 | [»] | |
5MFZ | X-ray | 2.10 | A/B | 13-308 | [»] | |
5MGN | X-ray | 2.07 | A/B | 13-308 | [»] | |
5X16 | X-ray | 1.97 | A | 3-318 | [»] | |
5Y2F | X-ray | 2.53 | A | 3-318 | [»] | |
6HOY | X-ray | 1.70 | A/B | 13-308 | [»] | |
6QCD | X-ray | 1.84 | A/B | 13-308 | [»] | |
6QCE | X-ray | 1.90 | A/B | 13-308 | [»] | |
6QCH | X-ray | 2.10 | A/B | 13-308 | [»] | |
6QCJ | X-ray | 2.01 | A/B | 13-308 | [»] | |
SMRi | Q8N6T7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 119603, 204 interactors |
DIPi | DIP-47346N |
IntActi | Q8N6T7, 71 interactors |
MINTi | Q8N6T7 |
STRINGi | 9606.ENSP00000337332 |
Chemistry databases
BindingDBi | Q8N6T7 |
ChEMBLi | CHEMBL2163182 |
GuidetoPHARMACOLOGYi | 2712 |
PTM databases
iPTMneti | Q8N6T7 |
PhosphoSitePlusi | Q8N6T7 |
Polymorphism and mutation databases
BioMutai | SIRT6 |
DMDMi | 38258612 |
Proteomic databases
EPDi | Q8N6T7 |
jPOSTi | Q8N6T7 |
MassIVEi | Q8N6T7 |
MaxQBi | Q8N6T7 |
PaxDbi | Q8N6T7 |
PeptideAtlasi | Q8N6T7 |
PRIDEi | Q8N6T7 |
ProteomicsDBi | 72232 [Q8N6T7-1] 72233 [Q8N6T7-2] |
Protocols and materials databases
Antibodypediai | 11389, 676 antibodies |
DNASUi | 51548 |
Genome annotation databases
Ensembli | ENST00000305232; ENSP00000305310; ENSG00000077463 [Q8N6T7-2] ENST00000337491; ENSP00000337332; ENSG00000077463 [Q8N6T7-1] |
GeneIDi | 51548 |
KEGGi | hsa:51548 |
UCSCi | uc002lzo.4, human [Q8N6T7-1] |
Organism-specific databases
CTDi | 51548 |
DisGeNETi | 51548 |
EuPathDBi | HostDB:ENSG00000077463.14 |
GeneCardsi | SIRT6 |
HGNCi | HGNC:14934, SIRT6 |
HPAi | ENSG00000077463, Low tissue specificity |
MIMi | 606211, gene |
neXtProti | NX_Q8N6T7 |
OpenTargetsi | ENSG00000077463 |
Orphaneti | 580933, Lethal brain and heart developmental defects |
PharmGKBi | PA37939 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1905, Eukaryota |
GeneTreei | ENSGT00940000160088 |
HOGENOMi | CLU_023643_6_0_1 |
InParanoidi | Q8N6T7 |
OMAi | NVLDWEH |
OrthoDBi | 1503290at2759 |
PhylomeDBi | Q8N6T7 |
TreeFami | TF106184 |
Enzyme and pathway databases
PathwayCommonsi | Q8N6T7 |
Reactomei | R-HSA-1912408, Pre-NOTCH Transcription and Translation R-HSA-5693607, Processing of DNA double-strand break ends |
SIGNORi | Q8N6T7 |
Miscellaneous databases
BioGRID-ORCSi | 51548, 9 hits in 856 CRISPR screens |
ChiTaRSi | SIRT6, human |
EvolutionaryTracei | Q8N6T7 |
GeneWikii | SIRT6 |
GenomeRNAii | 51548 |
Pharosi | Q8N6T7, Tchem |
PROi | PR:Q8N6T7 |
RNActi | Q8N6T7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000077463, Expressed in mucosa of transverse colon and 180 other tissues |
ExpressionAtlasi | Q8N6T7, baseline and differential |
Genevisiblei | Q8N6T7, HS |
Family and domain databases
IDEALi | IID00486 |
InterProi | View protein in InterPro IPR029035, DHS-like_NAD/FAD-binding_dom IPR003000, Sirtuin IPR026590, Ssirtuin_cat_dom |
Pfami | View protein in Pfam PF02146, SIR2, 2 hits |
SUPFAMi | SSF52467, SSF52467, 1 hit |
PROSITEi | View protein in PROSITE PS50305, SIRTUIN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SIR6_HUMAN | |
Accessioni | Q8N6T7Primary (citable) accession number: Q8N6T7 Secondary accession number(s): B2RCD0 Q9UQD1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 31, 2003 |
Last sequence update: | October 31, 2003 | |
Last modified: | December 2, 2020 | |
This is version 169 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations