NAD-dependent protein deacetylase sirtuin-2
Name | NAD-dependent protein deacetylase sirtuin-2 |
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Synonyms | 3.5.1.- Regulatory protein SIR2 homolog 2 SIR2-like protein 2 SIR2L SIR2L2 |
Gene Name | SIRT2 |
Organism | Human |
Amino acid sequence | >lcl|BSEQ0009282|NAD-dependent protein deacetylase sirtuin-2 MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKERLLD ELTLEGVARYMQSERCRRVICLVGAGISTSAGIPDFRSPSTGLYDNLEKYHLPYPEAIFE ISYFKKHPEPFFALAKELYPGQFKPTICHYFMRLLKDKGLLLRCYTQNIDTLERIAGLEQ EDLVEAHGTFYTSHCVSASCRHEYPLSWMKEKIFSEVTPKCEDCQSLVKPDIVFFGESLP ARFFSCMQSDFLKVDLLLVMGTSLQVQPFASLISKAPLSTPRLLINKEKAGQSDPFLGMI MGLGGGMDFDSKKAYRDVAWLGECDQGCLALAELLGWKKELEDLVRREHASIDAQSGAGV PNPSTSASPKKSPPPAKDEARTTEREKPQ |
Number of residues | 389 |
Molecular Weight | 43181.7 |
Theoretical pI | None |
GO Classification |
Functions
transcription factor binding NAD-dependent protein deacetylase activity histone deacetylase binding tubulin deacetylase activity protein deacetylase activity histone deacetylase activity zinc ion binding NAD+ binding ubiquitin binding histone acetyltransferase binding NAD-dependent histone deacetylase activity chromatin binding NAD-dependent histone deacetylase activity (H4-K16 specific) Processes
chromatin silencing at rDNA ripoptosome assembly involved in necroptotic process cellular response to oxidative stress negative regulation of reactive oxygen species metabolic process transcription, DNA-templated cell division tubulin deacetylation phosphatidylinositol 3-kinase signaling innate immune response negative regulation of striated muscle tissue development positive regulation of cell division cellular response to epinephrine stimulus cellular lipid catabolic process mitotic nuclear division histone H3 deacetylation negative regulation of transcription from RNA polymerase II promoter in response to hypoxia negative regulation of fat cell differentiation histone deacetylation hepatocyte growth factor receptor signaling pathway cellular response to caloric restriction negative regulation of cell proliferation histone H4 deacetylation peptidyl-lysine deacetylation response to redox state gene silencing negative regulation of autophagy cellular response to molecule of bacterial origin positive regulation of transcription from RNA polymerase II promoter protein deacetylation positive regulation of attachment of spindle microtubules to kinetochore positive regulation of DNA binding chromatin silencing chromatin silencing at telomere positive regulation of execution phase of apoptosis negative regulation of transcription, DNA-templated myelination in peripheral nervous system negative regulation of transcription from RNA polymerase II promoter positive regulation of meiotic nuclear division substantia nigra development negative regulation of defense response to bacterium protein kinase B signaling protein ADP-ribosylation positive regulation of oocyte maturation positive regulation of proteasomal ubiquitin-dependent protein catabolic process cellular response to hepatocyte growth factor stimulus negative regulation of NLRP3 inflammasome complex assembly regulation of cell cycle positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia negative regulation of protein catabolic process regulation of phosphorylation regulation of myelination negative regulation of oligodendrocyte progenitor proliferation meiotic cell cycle regulation of exit from mitosis proteasome-mediated ubiquitin-dependent protein catabolic process autophagy cellular response to hypoxia negative regulation of peptidyl-threonine phosphorylation Components
lateral loop nuclear heterochromatin centrosome cytoplasm glial cell projection microtubule meiotic spindle perikaryon spindle nucleus paranodal junction chromatin silencing complex mitotic spindle centriole chromosome paranode region of axon cytosol midbody plasma membrane myelin sheath growth cone juxtaparanode region of axon perinuclear region of cytoplasm Schmidt-Lanterman incisure |
General Function | Zinc ion binding |
Specific Function | NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. 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. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by SETD8 leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates SETD8 modulating SETD8 chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. 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. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor.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. |
Transmembrane Regions | |
GenBank Protein ID | |
UniProtKB ID | Q8IXJ6 |
UniProtKB Entry Name | SIR2_HUMAN |
Cellular Location | Nucleus |
Gene sequence | >lcl|BSEQ0013716|NAD-dependent protein deacetylase sirtuin-2 (SIRT2) ATGGACTTCCTGCGGAACTTATTCTCCCAGACGCTCAGCCTGGGCAGCCAGAAGGAGCGT CTGCTGGACGAGCTGACCTTGGAAGGGGTGGCCCGGTACATGCAGAGCGAACGCTGTCGC AGAGTCATCTGTTTGGTGGGAGCTGGAATCTCCACATCCGCAGGCATCCCCGACTTTCGC TCTCCATCCACCGGCCTCTATGACAACCTAGAGAAGTACCATCTTCCCTACCCAGAGGCC ATCTTTGAGATCAGCTATTTCAAGAAACATCCGGAACCCTTCTTCGCCCTCGCCAAGGAA CTCTATCCTGGGCAGTTCAAGCCAACCATCTGTCACTACTTCATGCGCCTGCTGAAGGAC AAGGGGCTACTCCTGCGCTGCTACACGCAGAACATAGATACCCTGGAGCGAATAGCCGGG CTGGAACAGGAGGACTTGGTGGAGGCGCACGGCACCTTCTACACATCACACTGCGTCAGC GCCAGCTGCCGGCACGAATACCCGCTAAGCTGGATGAAAGAGAAGATCTTCTCTGAGGTG ACGCCCAAGTGTGAAGACTGTCAGAGCCTGGTGAAGCCTGATATCGTCTTTTTTGGTGAG AGCCTCCCAGCGCGTTTCTTCTCCTGTATGCAGTCAGACTTCCTGAAGGTGGACCTCCTC CTGGTCATGGGTACCTCCTTGCAGGGACGTGGCCTGGCTGGGTGA |
GenBank Gene ID | |
GeneCard ID | None |
GenAtlas ID | |
HGNC ID | HGNC:10886 |
Chromosome Location | 19 |
Locus | None |
References |
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Related FRC
FRCD ID | Name | Exact Mass | Structure |
---|---|---|---|
Ketoconazole |
531.434 |
||
Niacinamide |
122.127 |
||
Ethanolamine |
61.084 |