|
SIRT2
an NAD-dependent protein deacetylase. Deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors and metabolic enzymes. Histone deacetylation is generally associated with transcriptional repression. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA. Interacts with HDAC6, suggesting that these proteins belong to a large complex that deacetylate the cytoskeleton. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Weakly expressed in several malignancies including breast, liver, brain, kidney and prostate cancers compared to normal tissues. Weakly expressed in glioma cell lines compared to normal brain tissues. Down-regulated in many gliomas suggesting that it may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network. Five alternatively spliced human isoforms have been reported. Isoform 1: Deacetylates EP300, alpha-tubulin and histone H3 and H4. Isoform 2: Deacetylates EP300, alpha-tubulin and histone H3 and H4. Isoform 5: Lacks deacetylation activity. Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Isoform 1 is expressed in heart, liver and skeletal muscle, weakly expressed in the cortex. Isoform 2 is strongly expressed in the cortex, weakly expressed in heart and liver. Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide.Belongs to the sirtuin family. Class I subfamily. Note: This description may include information from UniProtKB.
|
| Protein type: Deacetylase; EC 3.5.1.- |
| Chromosomal Location of human Ortholog: 19q13.2 |
|
Cellular Component:
centriole; centrosome; chromatin silencing complex; chromosome; chromosome, telomeric region; cytoplasm; cytosol; glial cell projection; growth cone; heterochromatin; juxtaparanode region of axon; lateral loop; meiotic spindle; microtubule; midbody; mitochondrion; mitotic spindle; myelin sheath; nucleolus; nucleus; paranodal junction; paranode region of axon; perikaryon; perinuclear region of cytoplasm; plasma membrane; Schmidt-Lanterman incisure; spindle
|
|
Molecular Function:
chromatin binding; DNA-binding transcription factor binding; histone acetyltransferase binding; histone deacetylase activity; histone deacetylase binding; NAD+ ADP-ribosyltransferase activity; NAD+ binding; NAD+-protein ADP-ribosyltransferase activity; NAD-dependent histone deacetylase activity; NAD-dependent histone H4K16 deacetylase activity; NAD-dependent protein deacetylase activity; NAD-dependent protein demyristoylase activity; NAD-dependent protein depalmitoylase activity; protein binding; protein lysine deacetylase activity; transcription factor binding; tubulin deacetylase activity; ubiquitin binding; zinc ion binding
|
|
Biological Process:
autophagy; cell division; cellular lipid catabolic process; cellular response to caloric restriction; cellular response to epinephrine stimulus; cellular response to hypoxia; cellular response to oxidative stress; epigenetic regulation of gene expression; heterochromatin formation; histone deacetylation; innate immune response; meiotic cell cycle; mitotic nuclear membrane reassembly; myelination in peripheral nervous system; negative regulation of autophagy; negative regulation of DNA-templated transcription; negative regulation of fat cell differentiation; negative regulation of NLRP3 inflammasome complex assembly; negative regulation of oligodendrocyte progenitor proliferation; negative regulation of peptidyl-threonine phosphorylation; negative regulation of protein catabolic process; negative regulation of reactive oxygen species metabolic process; negative regulation of striated muscle tissue development; negative regulation of transcription by RNA polymerase II; negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; NLRP3 inflammasome complex assembly; peptidyl-lysine deacetylation; positive regulation of attachment of spindle microtubules to kinetochore; positive regulation of cell division; positive regulation of DNA binding; positive regulation of execution phase of apoptosis; positive regulation of fatty acid biosynthetic process; positive regulation of meiotic nuclear division; positive regulation of oocyte maturation; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia; positive regulation of transcription by RNA polymerase II; post-translational protein modification; proteasome-mediated ubiquitin-dependent protein catabolic process; protein deacetylation; rDNA heterochromatin formation; regulation of cell cycle; regulation of exit from mitosis; regulation of myelination; regulation of phosphorylation; response to redox state; subtelomeric heterochromatin formation; tubulin deacetylation
|
|
Reference #:
Q8IXJ6
(UniProtKB)
|
|
Alt. Names/Synonyms: NAD-dependent deacetylase sirtuin-2; NAD-dependent protein deacetylase sirtuin-2; Regulatory protein SIR2 homolog 2; silencing information regulator 2-like; silent information regulator 2; SIR2; SIR2-like protein 2; sir2-related protein type 2; SIR2L; SIR2L2; SIRT2; sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae); sirtuin 2; sirtuin type 2
|
|
Gene Symbols: SIRT2
|
|
Molecular weight:
43,182 Da
|
|
Basal Isoelectric point:
5.22
Predict pI for various phosphorylation states
|
|
CST Pathways:
Apoptosis Regulation
|
Mitochondrial Control of Apoptosis
|
Protein Acetylation
|
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
|
