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NAD-dependent protein deacetylase sirtuin-2



Rattus norvegicus (Rat)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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 with both 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. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. 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-330 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.3 Publications


Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo.By similarity

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation


Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation (By similarity).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei150Proton acceptorPROSITE-ProRule annotation1
Metal bindingi158ZincPROSITE-ProRule annotation1
Metal bindingi163ZincPROSITE-ProRule annotation1
Metal bindingi184ZincPROSITE-ProRule annotation1
Metal bindingi187ZincPROSITE-ProRule annotation1
Binding sitei287NAD; via amide nitrogenBy similarity1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi47 – 67NADBy similarityAdd BLAST21
Nucleotide bindingi130 – 133NADBy similarity4
Nucleotide bindingi224 – 226NADBy similarity3
Nucleotide bindingi249 – 251NADBy similarity3

GO - Molecular functioni

GO - Biological processi


Molecular functionHydrolase
Biological processAutophagy, Cell cycle, Cell division, Differentiation, Meiosis, Mitosis, Neurogenesis, Transcription, Transcription regulation
LigandMetal-binding, NAD, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-2 (EC:3.5.1.-)
Alternative name(s):
Regulatory protein SIR2 homolog 2
SIR2-like protein 2
Gene namesi
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi621481. Sirt2.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm
  • Cytoplasmperinuclear region
  • Perikaryon
  • Myelin membrane
  • Cell projection
  • Cytoplasmcytoskeleton
  • Cell projectiongrowth cone By similarity
  • Cytoplasmcytoskeletonspindle By similarity
  • Chromosome By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole By similarity
  • Midbody By similarity

  • Note: Localizes in the cytoplasm during most of the cell cycle except in the G2/M transition and during mitosis, where it is localized in association with chromatin and induces deacetylation of histone at 'Lys-16' (H4K16ac). Colocalizes with CDK1 at centrosome during prophase and splindle fibers during metaphase. Colocalizes with Aurora kinase AURKA in centrioles during early prophase and growing mitotic spindle throughout metaphase. Colocalizes with Aurora kinase AURKB during cytokinesis with the midbody. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Shuttles between the cytoplasm and the nucleus through the CRM1 export pathway. Colocalizes with EP300 in the nucleus. Deacetylates FOXO3 in the cytoplasm. Colocalizes with Aurora kinase AURKA at centrosome. Colocalizes with microtubules. Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal neurons. Colocalizes with alpha-tubulin in neuronal growth cone. Colocalizes with KMT5A at mitotic foci. Localizes in the cytoplasm and nucleus of germinal vesicle (GV) stage oocytes. Colocalizes with alpha-tubulin on the meiotic spindle as the oocytes enter into metaphase, and also during meiotic anaphase and telophase, especially with the midbody (By similarity). Colocalizes with PLP1 in internodal regions of myelin sheat, at paranodal axoglial junction and Schmidt-Lanterman (SL) incisures. Colocalizes with PARD3 in internodal region of axons. Colocalizes with acetylated alpha-tubulin in cell projection processes during primary oligodendrocyte precursor (OLP) differentiation.By similarity

GO - Cellular componenti

  • centriole Source: UniProtKB
  • centrosome Source: UniProtKB
  • chromosome Source: UniProtKB
  • cytoplasm Source: RGD
  • cytosol Source: UniProtKB
  • glial cell projection Source: UniProtKB
  • growth cone Source: UniProtKB-SubCell
  • juxtaparanode region of axon Source: UniProtKB
  • lateral loop Source: UniProtKB
  • meiotic spindle Source: UniProtKB
  • microtubule Source: UniProtKB-KW
  • midbody Source: UniProtKB
  • mitotic spindle Source: UniProtKB
  • myelin sheath Source: UniProtKB
  • myelin sheath abaxonal region Source: RGD
  • nuclear heterochromatin Source: UniProtKB
  • nucleus Source: RGD
  • paranodal junction Source: UniProtKB
  • paranode region of axon Source: UniProtKB
  • perikaryon Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB-KW
  • Schmidt-Lanterman incisure Source: UniProtKB
  • spindle Source: UniProtKB
  • terminal loop Source: RGD

Keywords - Cellular componenti

Cell membrane, Cell projection, Chromosome, Cytoplasm, Cytoskeleton, Membrane, Microtubule, Nucleus

Pathology & Biotechi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi131N → A: Reduced deacetylase activity on alpha-tubulin and stimulates oligodendrocyte precursor (OLP) differentiation. 1 Publication1
Mutagenesisi133D → A: Reduced deacetylase activity on alpha-tubulin. 1 Publication1
Mutagenesisi150H → A: Reduced deacetylase activity on alpha-tubulin and stimulates oligodendrocyte precursor (OLP) differentiation. 1 Publication1

Chemistry databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002445361 – 350NAD-dependent protein deacetylase sirtuin-2Add BLAST350

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei16PhosphoserineCombined sources1
Modified residuei63PhosphoserineCombined sources1
Modified residuei170PhosphoserineCombined sources1
Modified residuei330PhosphoserineCombined sources1
Modified residuei334PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at phosphoserine and phosphothreonine. Phosphorylated at Ser-330 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression. Phosphorylated at Ser-330 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Phosphorylated by cyclin A/Cdk2 and p35-Cdk5 complexes and to a lesser extent by the cyclin D3/Cdk4 and cyclin B/Cdk1, in vitro. Dephosphorylated at Ser-330 by CDC14A and CDC14B around early anaphase (By similarity).By similarity
Acetylated by EP300; acetylation leads both to the decreased of SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-mediated down-regulation of TP53 transcriptional activity.By similarity
Ubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Tissue specificityi

Expressed in the cerebellum, cerebral cortex and cervival spinal cord. Expressed in Purkinje cells, oligodendrocytes and Schwann cells (at protein level). Expressed in the central nervous system (CNS).2 Publications


In oligodendrocytes during differentiation of CG-4 cells.1 Publication

Gene expression databases

ExpressionAtlasiQ5RJQ4. baseline and differential.
GenevisibleiQ5RJQ4. RN.


Subunit structurei

Homotrimer. Interacts (via both phosphorylated, unphosphorylated, active or inactive forms) with HDAC6; the interaction is necessary for the complex to interact with alpha-tubulin, suggesting that these proteins belong to a large complex that deacetylates the cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon serum-starvation or oxidative stress, leading to increased level of acetylated FOXO1 and induction of autophagy. Interacts with RELA; the interaction occurs in the cytoplasm and is increased in a TNF-alpha-dependent manner. Interacts with HOXA10; the interaction is direct. Interacts with YWHAB and YWHAG; the interactions occur in a AKT-dependent manner and increase SIRT2-dependent TP53 deacetylation. Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions increase SIRT2 stability and deacetylation activity. Interacts (phosphorylated form) with KMT5A; the interaction is direct, stimulates KMT5A-mediated methyltransferase activity on histone at 'Lys-20' (H4K20me1) and is increased in a H2O2-induced oxidative stress-dependent manner. Interacts with G6PD; the interaction is enhanced by H2O2 treatment. Interacts (via C-terminus region) with EP300. Interacts with a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA, CDC20, CDK5R1 (p35 form), CDK5, FOXO3, FZR1 and HIF1A. Associates with microtubule in primary cortical mature neurons (By similarity).By similarity

Protein-protein interaction databases

BioGridi262752. 1 interactor.


3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini28 – 303Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST276


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni79 – 83Peptide inhibitor bindingBy similarity5
Regioni195 – 264Peptide inhibitor bindingBy similarityAdd BLAST70


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 14Nuclear export signalBy similarityAdd BLAST11

Sequence similaritiesi

Belongs to the sirtuin family. Class I subfamily.Curated

Phylogenomic databases

eggNOGiKOG2682. Eukaryota.
COG0846. LUCA.

Family and domain databases

Gene3Di3.40.50.1220. 1 hit.
InterProiView protein in InterPro
IPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
PfamiView protein in Pfam
PF02146. SIR2. 1 hit.
PIRSFiPIRSF037938. SIR2_euk. 1 hit.
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiView protein in PROSITE
PS50305. SIRTUIN. 1 hit.


Sequence statusi: Complete.

Q5RJQ4-1 [UniParc]FASTAAdd to basket

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Mass (Da):39,319
Last modified:December 21, 2004 - v1

Sequence databases

Select the link destinations:
Links Updated
BC086545 mRNA. Translation: AAH86545.1.
RefSeqiNP_001008369.1. NM_001008368.1.

Genome annotation databases

EnsembliENSRNOT00000064153; ENSRNOP00000059450; ENSRNOG00000020102.
UCSCiRGD:621481. rat.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiSIR2_RAT
AccessioniPrimary (citable) accession number: Q5RJQ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: December 21, 2004
Last modified: June 7, 2017
This is version 110 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome


  1. SIMILARITY comments
    Index of protein domains and families