NAD-dependent protein deacetylase sirtuin-2

Details

Name
NAD-dependent protein deacetylase sirtuin-2
Synonyms
  • 3.5.1.-
  • Regulatory protein SIR2 homolog 2
  • SIR2-like protein 2
  • SIR2L
  • SIR2L2
Gene Name
SIRT2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052129|NAD-dependent protein deacetylase sirtuin-2
MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKERLLD
ELTLEGVARYMQSERCRRVICLVGAGISTSAGIPDFRSPSTGLYDNLEKYHLPYPEAIFE
ISYFKKHPEPFFALAKELYPGQFKPTICHYFMRLLKDKGLLLRCYTQNIDTLERIAGLEQ
EDLVEAHGTFYTSHCVSASCRHEYPLSWMKEKIFSEVTPKCEDCQSLVKPDIVFFGESLP
ARFFSCMQSDFLKVDLLLVMGTSLQVQPFASLISKAPLSTPRLLINKEKAGQSDPFLGMI
MGLGGGMDFDSKKAYRDVAWLGECDQGCLALAELLGWKKELEDLVRREHASIDAQSGAGV
PNPSTSASPKKSPPPAKDEARTTEREKPQ
Number of residues
389
Molecular Weight
43181.7
Theoretical pI
Not Available
GO Classification
Functions
chromatin binding / histone acetyltransferase binding / histone deacetylase activity / histone deacetylase binding / NAD-dependent histone deacetylase activity / NAD-dependent histone deacetylase activity (H4-K16 specific) / NAD-dependent protein deacetylase activity / NAD+ binding / protein deacetylase activity / transcription factor binding / tubulin deacetylase activity / ubiquitin binding / zinc ion binding
Processes
autophagy / cell division / cellular lipid catabolic process / cellular response to caloric restriction / cellular response to epinephrine stimulus / cellular response to hepatocyte growth factor stimulus / cellular response to hypoxia / cellular response to molecule of bacterial origin / cellular response to oxidative stress / chromatin silencing / chromatin silencing at rDNA / chromatin silencing at telomere / gene silencing / hepatocyte growth factor receptor signaling pathway / histone deacetylation / histone H3 deacetylation / histone H4 deacetylation / innate immune response / meiotic cell cycle / myelination in peripheral nervous system / negative regulation of autophagy / negative regulation of cell population proliferation / negative regulation of defense response to bacterium / 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 / negative regulation of transcription, DNA-templated / peptidyl-lysine deacetylation / phosphatidylinositol 3-kinase signaling / 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 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 / proteasome-mediated ubiquitin-dependent protein catabolic process / protein ADP-ribosylation / protein deacetylation / protein kinase B signaling / regulation of cell cycle / regulation of exit from mitosis / regulation of myelination / regulation of phosphorylation / response to redox state / substantia nigra development / tubulin deacetylation
Components
centriole / centrosome / chromatin silencing complex / chromosome / chromosome, telomeric region / cytoplasm / cytosol / glial cell projection / growth cone / juxtaparanode region of axon / lateral loop / meiotic spindle / microtubule / midbody / mitochondrion / mitotic spindle / myelin sheath / nuclear heterochromatin / nucleolus / nucleus / paranodal junction / paranode region of axon / perikaryon / perinuclear region of cytoplasm / plasma membrane / Schmidt-Lanterman incisure / spindle
General 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 (PubMed:24177535, PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20587414, PubMed:21081649, PubMed:20543840, PubMed:22014574, PubMed:21726808, PubMed:21949390, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24940000, PubMed:24769394, PubMed:24681946). 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 KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). 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 (PubMed:23908241). 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 histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). 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 (PubMed:20543840). 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 (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187). Deacetylates also EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor (PubMed:22014574).
Specific Function
Chromatin binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0052130|NAD-dependent protein deacetylase sirtuin-2 (SIRT2)
ATGGCAGAGCCAGACCCCTCTCACCCTCTGGAGACCCAGGCAGGGAAGGTGCAGGAGGCT
CAGGACTCAGATTCAGACTCTGAGGGAGGAGCCGCTGGTGGAGAAGCAGACATGGACTTC
CTGCGGAACTTATTCTCCCAGACGCTCAGCCTGGGCAGCCAGAAGGAGCGTCTGCTGGAC
GAGCTGACCTTGGAAGGGGTGGCCCGGTACATGCAGAGCGAACGCTGTCGCAGAGTCATC
TGTTTGGTGGGAGCTGGAATCTCCACATCCGCAGGCATCCCCGACTTTCGCTCTCCATCC
ACCGGCCTCTATGACAACCTAGAGAAGTACCATCTTCCCTACCCAGAGGCCATCTTTGAG
ATCAGCTATTTCAAGAAACATCCGGAACCCTTCTTCGCCCTCGCCAAGGAACTCTATCCT
GGGCAGTTCAAGCCAACCATCTGTCACTACTTCATGCGCCTGCTGAAGGACAAGGGGCTA
CTCCTGCGCTGCTACACGCAGAACATAGATACCCTGGAGCGAATAGCCGGGCTGGAACAG
GAGGACTTGGTGGAGGCGCACGGCACCTTCTACACATCACACTGCGTCAGCGCCAGCTGC
CGGCACGAATACCCGCTAAGCTGGATGAAAGAGAAGATCTTCTCTGAGGTGACGCCCAAG
TGTGAAGACTGTCAGAGCCTGGTGAAGCCTGATATCGTCTTTTTTGGTGAGAGCCTCCCA
GCGCGTTTCTTCTCCTGTATGCAGTCAGACTTCCTGAAGGTGGACCTCCTCCTGGTCATG
GGTACCTCCTTGCAGGTGCAGCCCTTTGCCTCCCTCATCAGCAAGGCACCCCTCTCCACC
CCTCGCCTGCTCATCAACAAGGAGAAAGCTGGCCAGTCGGACCCTTTCCTGGGGATGATT
ATGGGCCTCGGAGGAGGCATGGACTTTGACTCCAAGAAGGCCTACAGGGACGTGGCCTGG
CTGGGTGAATGCGACCAGGGCTGCCTGGCCCTTGCTGAGCTCCTTGGATGGAAGAAGGAG
CTGGAGGACCTTGTCCGGAGGGAGCACGCCAGCATAGATGCCCAGTCGGGGGCGGGGGTC
CCCAACCCCAGCACTTCAGCTTCCCCCAAGAAGTCCCCGCCACCTGCCAAGGACGAGGCC
AGGACAACAGAGAGGGAGAAACCCCAGTGA
Chromosome Location
19
Locus
19q13.2
External Identifiers
ResourceLink
UniProtKB IDQ8IXJ6
UniProtKB Entry NameSIR2_HUMAN
HGNC IDHGNC:10886
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB15493CambinolexperimentalyesinhibitorDetails