NAD-dependent protein deacetylase sirtuin-2

NameNAD-dependent protein deacetylase sirtuin-2
Synonyms
  • 3.5.1.-
  • Regulatory protein SIR2 homolog 2
  • SIR2-like protein 2
  • SIR2L
  • SIR2L2
Gene NameSIRT2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009282|NAD-dependent protein deacetylase sirtuin-2
MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKERLLD
ELTLEGVARYMQSERCRRVICLVGAGISTSAGIPDFRSPSTGLYDNLEKYHLPYPEAIFE
ISYFKKHPEPFFALAKELYPGQFKPTICHYFMRLLKDKGLLLRCYTQNIDTLERIAGLEQ
EDLVEAHGTFYTSHCVSASCRHEYPLSWMKEKIFSEVTPKCEDCQSLVKPDIVFFGESLP
ARFFSCMQSDFLKVDLLLVMGTSLQVQPFASLISKAPLSTPRLLINKEKAGQSDPFLGMI
MGLGGGMDFDSKKAYRDVAWLGECDQGCLALAELLGWKKELEDLVRREHASIDAQSGAGV
PNPSTSASPKKSPPPAKDEARTTEREKPQ
Number of residues389
Molecular Weight43181.7
Theoretical pINot Available
GO Classification
Functions
  • zinc ion binding
  • NAD+ binding
  • histone deacetylase binding
  • protein deacetylase activity
  • chromatin binding
  • histone acetyltransferase binding
  • transcription factor binding
  • NAD-dependent histone deacetylase activity
  • NAD-dependent histone deacetylase activity (H4-K16 specific)
  • histone deacetylase activity
  • NAD-dependent protein deacetylase activity
  • tubulin deacetylase activity
  • ubiquitin binding
Processes
  • chromatin silencing at telomere
  • cellular response to hepatocyte growth factor stimulus
  • chromatin silencing at rDNA
  • ripoptosome assembly involved in necroptotic process
  • myelination in peripheral nervous system
  • regulation of phosphorylation
  • tubulin deacetylation
  • response to redox state
  • negative regulation of defense response to bacterium
  • autophagy
  • cellular response to epinephrine stimulus
  • positive regulation of DNA binding
  • negative regulation of NLRP3 inflammasome complex assembly
  • cellular response to oxidative stress
  • negative regulation of fat cell differentiation
  • negative regulation of transcription, DNA-templated
  • negative regulation of oligodendrocyte progenitor proliferation
  • innate immune response
  • substantia nigra development
  • negative regulation of peptidyl-threonine phosphorylation
  • mitotic nuclear division
  • histone H3 deacetylation
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  • negative regulation of reactive oxygen species metabolic process
  • negative regulation of cell proliferation
  • histone H4 deacetylation
  • regulation of cell cycle
  • negative regulation of protein catabolic process
  • negative regulation of striated muscle tissue development
  • positive regulation of transcription from RNA polymerase II promoter
  • proteasome-mediated ubiquitin-dependent protein catabolic process
  • negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
  • phosphatidylinositol 3-kinase signaling
  • peptidyl-lysine deacetylation
  • negative regulation of transcription from RNA polymerase II promoter
  • cell division
  • protein deacetylation
  • positive regulation of attachment of spindle microtubules to kinetochore
  • protein kinase B signaling
  • hepatocyte growth factor receptor signaling pathway
  • positive regulation of execution phase of apoptosis
  • histone deacetylation
  • negative regulation of autophagy
  • positive regulation of meiotic nuclear division
  • regulation of myelination
  • gene silencing
  • chromatin silencing
  • protein ADP-ribosylation
  • positive regulation of oocyte maturation
  • cellular response to hypoxia
  • cellular lipid catabolic process
  • cellular response to caloric restriction
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia
  • transcription, DNA-templated
  • cellular response to molecule of bacterial origin
  • meiotic cell cycle
  • regulation of exit from mitosis
  • positive regulation of cell division
Components
  • myelin sheath
  • perinuclear region of cytoplasm
  • nuclear heterochromatin
  • cytoplasm
  • Schmidt-Lanterman incisure
  • microtubule
  • nucleus
  • glial cell projection
  • chromosome
  • meiotic spindle
  • plasma membrane
  • paranodal junction
  • paranode region of axon
  • perikaryon
  • lateral loop
  • centrosome
  • spindle
  • growth cone
  • centriole
  • chromatin silencing complex
  • mitotic spindle
  • juxtaparanode region of axon
  • cytosol
  • midbody
General FunctionZinc ion binding
Specific FunctionNAD-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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ8IXJ6
UniProtKB Entry NameSIR2_HUMAN
Cellular LocationNucleus
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 IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:10886
Chromosome Location19
LocusNot Available
References
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