CPLM-017485

Genbank Nucleotide ID

NAD-dependent protein deacetylase sirtuin-6

Protein Synonyms/Alias

Regulatory protein SIR2 homolog 6; SIR2-like protein 6

Homo sapiens (Human)

Position	Peptide	Type	References
15	GLSPYADKGKCGLPE	ubiquitination	[1]
17	SPYADKGKCGLPEIF	ubiquitination	[1]
81	EERGLAPKFDTTFES	ubiquitination	[1]
128	RSGFPRDKLAELHGN	ubiquitination	[1]
170	GRLCTVAKARGLRAC	ubiquitination	[1]
245	IVNLQPTKHDRHADL	ubiquitination	[1]
267	EVMTRLMKHLGLEIP	ubiquitination	[1, 2, 3]

[1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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.

DOMAIN 35 274 Deacetylase sirtuin-type.
NP_BIND 52 71 NAD.
NP_BIND 113 116 NAD.
NP_BIND 214 216 NAD.
NP_BIND 240 242 NAD.
ACT_SITE 133 133 Proton acceptor.
METAL 141 141 Zinc.
METAL 144 144 Zinc.
METAL 166 166 Zinc.
METAL 177 177 Zinc.
BINDING 258 258 NAD; via amide nitrogen.
MOD_RES 2 2 N-acetylserine.
MOD_RES 303 303 Phosphoserine.
MOD_RES 330 330 Phosphoserine.

3D-structure; Acetylation; Alternative splicing; Complete proteome; Hydrolase; Metal-binding; NAD; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Zinc.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005724; C:nuclear telomeric heterochromatin; IDA:UniProtKB.
GO:0005654; C:nucleoplasm; IDA:UniProtKB.
GO:0003956; F:NAD(P)+-protein-arginine ADP-ribosyltransferase activity; ISS:UniProtKB.
GO:0003950; F:NAD+ ADP-ribosyltransferase activity; TAS:BHF-UCL.
GO:0070403; F:NAD+ binding; ISS:UniProtKB.
GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IDA:UniProtKB.
GO:0008270; F:zinc ion binding; ISS:UniProtKB.
GO:0006471; P:protein ADP-ribosylation; ISS:UniProtKB.
GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.

IPR003000; Sirtuin.
IPR026590; Ssirtuin_cat_dom.