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Q8IXJ6 (SIR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NAD-dependent protein deacetylase sirtuin-2

EC=3.5.1.-
Alternative name(s):
Regulatory protein SIR2 homolog 2
SIR2-like protein 2
Gene names
Name:SIRT2
Synonyms:SIR2L, SIR2L2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length389 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.4 Ref.14 Ref.15 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50

Isoform 1:Deacetylates EP300, alpha-tubulin and histone H3 and H4. Ref.4 Ref.14 Ref.15 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50

Isoform 2:Deacetylates EP300, alpha-tubulin and histone H3 and H4. Ref.4 Ref.14 Ref.15 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50

Isoform 5:Lacks deacetylation activity. Ref.4 Ref.14 Ref.15 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50

Catalytic activity

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.13 Ref.20

Cofactor

Binds 1 zinc ion per subunit.

Enzyme regulation

Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation. Ref.27 Ref.53

Subunit structure

Interacts with CDC20, FOXO3 and FZR1. Associates with microtubule in primary cortical mature neurons By similarity. Homotrimer. Isoform 1 and isoform 2 interact (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 SETD8 isoform 2;the interaction is direct, stimulates SETD8-mediated methyltransferase activity on histone at 'Lys-20' (H4K20me1) and is increased in a H2O(2)-induced oxidative stress-dependent manner. Interacts with G6PD; the interaction is enhanced by H2O2 treatment. Interacts with a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A. Isoform 1, isoform 2 and isoform 5 interact (via C-terminus region) with EP300. Ref.4 Ref.14 Ref.17 Ref.20 Ref.22 Ref.25 Ref.26 Ref.27 Ref.29 Ref.36 Ref.37 Ref.41 Ref.45 Ref.46 Ref.49 Ref.50

Subcellular location

Nucleus. Cytoplasmperinuclear region. Cytoplasm. Cytoplasmcytoskeleton. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole. Cytoplasmcytoskeletonspindle. Midbody. Chromosome. Perikaryon By similarity. Cell projection By similarity. Cell projectiongrowth cone By similarity. Myelin membrane By similarity. Note: Deacetylates FOXO3 in the cytoplasm. Colocalizes with PLP1 in internodal regions, at paranodal axoglial junction and Schmidt-Lanterman incisures of myelin sheat. Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal neurons. Colocalizes with alpha-tubulin in neuronal growth cone. 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. 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. 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 SETD8 at mitotic foci. Colocalizes with CDK1 at centrosome during prophase and splindle fibers during metaphase. Colocalizes with Aurora kinase AURKA at centrosome during early prophase and in the centrioles and growing mitotic spindle throughout metaphase. Colocalizes with Aurora kinase AURKB during cytokinesis with the midbody. Colocalizes with microtubules. 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. Translocates to the nucleus and chromatin upon bacterium Listeria monocytogenes infection in interphase cells. Ref.2 Ref.4 Ref.11 Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.24 Ref.25 Ref.30 Ref.36 Ref.43 Ref.46 Ref.48 Ref.50

Isoform 1: Cytoplasm. Nucleus. Note: Predominantly localized in the cytoplasmic. Ref.2 Ref.4 Ref.11 Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.24 Ref.25 Ref.30 Ref.36 Ref.43 Ref.46 Ref.48 Ref.50

Isoform 2: Cytoplasm. Nucleus. Note: Predominantly localized in the cytoplasmic. Ref.2 Ref.4 Ref.11 Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.24 Ref.25 Ref.30 Ref.36 Ref.43 Ref.46 Ref.48 Ref.50

Isoform 5: Cytoplasm. Nucleus. Note: Predominantly localized in the nucleus. Ref.2 Ref.4 Ref.11 Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.24 Ref.25 Ref.30 Ref.36 Ref.43 Ref.46 Ref.48 Ref.50

Tissue specificity

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. 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 (at protein level). Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. 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. Ref.1 Ref.2 Ref.16 Ref.24 Ref.38 Ref.39

Developmental stage

Peaks during mitosis. After mitosis, it is probably degraded by the 26S proteasome. Ref.15

Induction

Up-regulated in response to low levels of glucose and anoxia-reoxygenation stress. Up-regulated by trichostatin A. Down-regulated in response to high levels of glucose. Down-regulated by histone deacetylation in several tumors. Ref.24 Ref.27 Ref.28 Ref.40 Ref.53

Post-translational modification

Phosphorylated at phosphoserine and phosphothreonine. Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression. Phosphorylated at Ser-368 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-368 by CDC14A and CDC14B around early anaphase. Ref.15 Ref.21 Ref.22 Ref.29

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. Ref.4 Ref.27

Ubiquitinated. Ref.15 Ref.22

Sequence similarities

Belongs to the sirtuin family. Class I subfamily.

Contains 1 deacetylase sirtuin-type domain.

Sequence caution

The sequence AAD45971.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAF67015.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Biological processAutophagy
Cell cycle
Cell division
Differentiation
Immunity
Innate immunity
Meiosis
Mitosis
Neurogenesis
Transcription
Transcription regulation
   Cellular componentCell membrane
Cell projection
Chromosome
Cytoplasm
Cytoskeleton
Membrane
Microtubule
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseNeurodegeneration
   LigandMetal-binding
NAD
Zinc
   Molecular functionHydrolase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular lipid catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to epinephrine stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to hepatocyte growth factor stimulus

Inferred from direct assay Ref.48. Source: UniProtKB

cellular response to molecule of bacterial origin

Inferred from direct assay Ref.48. Source: UniProtKB

chromatin silencing

Non-traceable author statement Ref.15. Source: UniProtKB

chromatin silencing at rDNA

Non-traceable author statement Ref.51. Source: UniProtKB

chromatin silencing at telomere

Non-traceable author statement Ref.51. Source: UniProtKB

gene silencing

Non-traceable author statement Ref.1. Source: UniProtKB

hepatocyte growth factor receptor signaling pathway

Inferred from direct assay Ref.48. Source: UniProtKB

histone H3 deacetylation

Inferred from mutant phenotype Ref.48. Source: UniProtKB

histone H4 deacetylation

Inferred from direct assay Ref.20Ref.21. Source: UniProtKB

histone deacetylation

Inferred from direct assay Ref.4. Source: UniProtKB

mitotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

myelination in peripheral nervous system

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from mutant phenotype Ref.21. Source: UniProtKB

negative regulation of defense response to bacterium

Inferred from mutant phenotype Ref.48. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of oligodendrocyte progenitor proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of striated muscle tissue development

Inferred from direct assay PubMed 12887892. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.27. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12887892. Source: UniProtKB

peptidyl-lysine deacetylation

Inferred from direct assay Ref.47. Source: UniProtKB

phosphatidylinositol 3-kinase signaling

Inferred from mutant phenotype Ref.48. Source: UniProtKB

positive regulation of attachment of spindle microtubules to kinetochore

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell division

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of meiosis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of oocyte maturation

Inferred from sequence or structural similarity. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 21841822. Source: UniProtKB

protein ADP-ribosylation

Non-traceable author statement Ref.1. Source: UniProtKB

protein deacetylation

Inferred from direct assay PubMed 17172643Ref.37Ref.41Ref.4. Source: UniProtKB

protein kinase B signaling

Inferred from mutant phenotype Ref.48. Source: UniProtKB

regulation of cell cycle

Inferred from mutant phenotype Ref.25. Source: UniProtKB

regulation of exit from mitosis

Non-traceable author statement Ref.15. Source: UniProtKB

regulation of myelination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of phosphorylation

Non-traceable author statement Ref.15. Source: UniProtKB

response to redox state

Non-traceable author statement PubMed 12887892. Source: UniProtKB

substantia nigra development

Inferred from expression pattern PubMed 22926577. Source: UniProt

tubulin deacetylation

Inferred from direct assay Ref.27Ref.4. Source: UniProtKB

   Cellular_componentSchmidt-Lanterman incisure

Inferred from sequence or structural similarity. Source: UniProtKB

centriole

Inferred from direct assay Ref.25. Source: UniProtKB

centrosome

Inferred from direct assay Ref.21Ref.25. Source: UniProtKB

chromatin silencing complex

Non-traceable author statement Ref.15. Source: UniProtKB

chromosome

Inferred from direct assay Ref.20. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.15Ref.17Ref.18Ref.20Ref.25Ref.37Ref.48Ref.4. Source: UniProtKB

glial cell projection

Inferred from sequence or structural similarity. Source: UniProtKB

juxtaparanode region of axon

Inferred from sequence or structural similarity. Source: UniProtKB

lateral loop

Inferred from sequence or structural similarity. Source: UniProtKB

meiotic spindle

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule

Inferred from direct assay Ref.14. Source: UniProtKB

midbody

Inferred from direct assay Ref.25. Source: UniProtKB

mitotic spindle

Inferred from direct assay Ref.21. Source: UniProtKB

myelin sheath

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear heterochromatin

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay Ref.17Ref.20Ref.25Ref.48Ref.4. Source: UniProtKB

paranodal junction

Inferred from sequence or structural similarity. Source: UniProtKB

paranode region of axon

Inferred from sequence or structural similarity. Source: UniProtKB

perikaryon

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

spindle

Inferred from direct assay Ref.25. Source: UniProtKB

   Molecular_functionNAD+ binding

Inferred from direct assay Ref.51. Source: UniProtKB

NAD-dependent histone deacetylase activity

Inferred from direct assay Ref.51Ref.15Ref.4. Source: UniProtKB

NAD-dependent histone deacetylase activity (H4-K16 specific)

Inferred from direct assay Ref.20. Source: UniProtKB

NAD-dependent protein deacetylase activity

Inferred from direct assay Ref.27Ref.41Ref.47. Source: UniProtKB

chromatin binding

Inferred from direct assay Ref.48. Source: UniProtKB

histone acetyltransferase binding

Inferred from physical interaction PubMed 12887892. Source: UniProtKB

histone deacetylase activity

Inferred from direct assay Ref.21. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction Ref.14. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.38. Source: IntAct

protein deacetylase activity

Inferred from direct assay PubMed 17172643Ref.37. Source: UniProtKB

transcription factor binding

Inferred from physical interaction PubMed 12887892PubMed 15126506Ref.17Ref.37. Source: UniProtKB

tubulin deacetylase activity

Inferred from direct assay Ref.14Ref.27Ref.4. Source: UniProtKB

ubiquitin binding

Inferred from direct assay Ref.15. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.51. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IXJ6-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8IXJ6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: Missing.
Isoform 3 (identifier: Q8IXJ6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADM → MPLAECPSCRCLSSFRSV
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8IXJ6-4)

The sequence of this isoform differs from the canonical sequence as follows:
     266-271: VQPFAS → GRGLAG
     272-389: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q8IXJ6-5)

The sequence of this isoform differs from the canonical sequence as follows:
     6-76: PSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKERLLDELTLEGVARYMQSERC → R
Note: Lacks deacetylase activity, at least toward known SIRT2 targets.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.32
Chain2 – 389388NAD-dependent protein deacetylase sirtuin-2
PRO_0000110258

Regions

Domain65 – 340276Deacetylase sirtuin-type
Nucleotide binding84 – 10421NAD
Nucleotide binding167 – 1704NAD
Nucleotide binding261 – 2633NAD
Nucleotide binding286 – 2883NAD
Region116 – 1205Peptide inhibitor binding
Region232 – 30170Peptide inhibitor binding
Motif41 – 5111Nuclear export signal

Sites

Active site1871Proton acceptor
Metal binding1951Zinc
Metal binding2001Zinc
Metal binding2211Zinc
Metal binding2241Zinc
Binding site3241NAD; via amide nitrogen

Amino acid modifications

Modified residue21N-acetylalanine Ref.32
Modified residue3681Phosphoserine; by CDK2 (in a cyclin E-CDK2 complex); by CDK5 (in the cyclin p35-CDK5) Ref.21 Ref.22 Ref.29
Modified residue3721Phosphoserine Ref.22

Natural variations

Alternative sequence1 – 3838MAEPD…GEADM → MPLAECPSCRCLSSFRSV in isoform 3.
VSP_008726
Alternative sequence1 – 3737Missing in isoform 2.
VSP_008724
Alternative sequence6 – 7671PSHPL…QSERC → R in isoform 5.
VSP_055328
Alternative sequence266 – 2716VQPFAS → GRGLAG in isoform 4.
VSP_008727
Alternative sequence272 – 389118Missing in isoform 4.
VSP_008728

Experimental info

Mutagenesis531S → A: Reduces deacetylase activity. Ref.22
Mutagenesis971R → A: No effect on deacetylase activity. Ref.51
Mutagenesis981S → A: Inhibits deacetylase activity. Ref.22
Mutagenesis1001S → A: Reduces deacetylase activity. Ref.22
Mutagenesis1161E → A: Reduces binding for the peptide inhibitor S2iL5. Ref.53
Mutagenesis1201E → A: Reduces binding for the peptide inhibitor S2iL5. Ref.53
Mutagenesis1671Q → A: Reduces deacetylase activity. Inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell formation in response to mitotic stress; when associated with A-168 and A-187. Ref.24 Ref.51
Mutagenesis1681N → A: Abolishes deacetylation of alpha-tubulin. Inhibits deacetylation of histone H3 at 'Lys-18'. Inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell formation in response to mitotic stress; when associated with A-167 and A-187. Ref.14 Ref.24 Ref.48 Ref.49 Ref.51
Mutagenesis1701D → A or N: Reduces deacetylase activity. Ref.51
Mutagenesis1871H → Y or A: Inhibits histone, alpha-tubulin, FZR1 and CDC20 deacetylation activities. No effect on CDK2-dependent phosphorylation. Does not inhibit interaction with HDAC6, HIF1A and the cyclin E-CDK2 complex. Inhibits interaction with SETD8. Abolishes deacetylation, dimeric formation and enzymatic activity increase of G6PD. Prevents histone H4 methylation at 'Lys-20'(H4K20me1) in metaphase chromosomes. Inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell formation in response to mitotic stress; when associated with A-167 and A-168. Ref.1 Ref.13 Ref.14 Ref.15 Ref.21 Ref.22 Ref.24 Ref.25 Ref.38 Ref.50 Ref.51
Mutagenesis2441F → A: Reduces strongly binding for the peptide inhibitor S2iL5. Ref.53
Mutagenesis2651Q → A: Reduces binding for the peptide inhibitor S2iL5. Ref.53
Mutagenesis2711S → A: Reduces binding for the peptide inhibitor S2iL5. Ref.53
Mutagenesis2791S → A: Reduces deacetylase activity. Ref.22
Mutagenesis2801T → A: Reduces deacetylase activity. Ref.22
Mutagenesis2941D → A: Reduces binding for the peptide inhibitor S2iL5. Ref.53
Mutagenesis3111S → A: Reduces deacetylase activity. Ref.22
Mutagenesis3151Y → A: Reduces deacetylase activity. Ref.22
Mutagenesis3641S → A: Abolishes CDK2-dependent phosphorylation. Ref.22
Mutagenesis3681S → A: Does not affect deacetylase activity. Abolishes CDK2-dependent phosphorylation. Inhibits cellular proliferation delay in the early metaphase to prevent chromosomal instability. Does not inhibit interaction with a cyclin E-CDK2 complex. Does not inhibit interaction with HDAC6 and ubiquitination. Inhibits cell adhesion and migration and neurite outgrowth. Inhibits deacetylase activity; when associated with A-372. Ref.21 Ref.22 Ref.29
Mutagenesis3681S → D: Abolishes CDK2-dependent phosphorylation. Inhibits interaction with a cyclin E-CDK2 complex. Reduces strongly histone deacetylation activity. Ref.21 Ref.22 Ref.29
Mutagenesis3681S → E: Abolishes CDK2-dependent phosphorylation. Ref.21 Ref.22 Ref.29
Mutagenesis3721S → A: Reduces phosphorylation. Does not inhibit interaction with HDAC6, ubiquitination and deacetylase activity. Inhibits deacetylase activity; when associated with A-368. Ref.22
Sequence conflict1991S → N Ref.6
Sequence conflict2191P → L in CAD43717. Ref.5

Secondary structure

................................................................ 389
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 31, 2003. Version 2.
Checksum: A392442A8F6316F1

FASTA38943,182
        10         20         30         40         50         60 
MAEPDPSHPL ETQAGKVQEA QDSDSDSEGG AAGGEADMDF LRNLFSQTLS LGSQKERLLD 

        70         80         90        100        110        120 
ELTLEGVARY MQSERCRRVI CLVGAGISTS AGIPDFRSPS TGLYDNLEKY HLPYPEAIFE 

       130        140        150        160        170        180 
ISYFKKHPEP FFALAKELYP GQFKPTICHY FMRLLKDKGL LLRCYTQNID TLERIAGLEQ 

       190        200        210        220        230        240 
EDLVEAHGTF YTSHCVSASC RHEYPLSWMK EKIFSEVTPK CEDCQSLVKP DIVFFGESLP 

       250        260        270        280        290        300 
ARFFSCMQSD FLKVDLLLVM GTSLQVQPFA SLISKAPLST PRLLINKEKA GQSDPFLGMI 

       310        320        330        340        350        360 
MGLGGGMDFD SKKAYRDVAW LGECDQGCLA LAELLGWKKE LEDLVRREHA SIDAQSGAGV 

       370        380 
PNPSTSASPK KSPPPAKDEA RTTEREKPQ 

« Hide

Isoform 2 [UniParc].

Checksum: FFED07DEF9E3416A
Show »

FASTA35239,515
Isoform 3 [UniParc].

Checksum: 0805580CAAB59A51
Show »

FASTA36941,353
Isoform 4 [UniParc].

Checksum: FF4641368029BD94
Show »

FASTA27130,379
Isoform 5 [UniParc].

Checksum: 78A23E5456789A9D
Show »

FASTA31935,654

References

« Hide 'large scale' references
[1]"Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity."
Frye R.A.
Biochem. Biophys. Res. Commun. 260:273-279(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF HIS-187.
Tissue: Testis.
[2]"Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2."
Afshar G., Murnane J.P.
Gene 234:161-168(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"A novel seven transmembrane receptor induced during the early steps of astrocyte differentiation identified by differential expression."
De Smet C., Nishimori H., Furnari F.B., Boegler O., Huang H.-J.S., Cavenee W.K.
J. Neurochem. 81:575-588(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]"Constitutive nuclear localization of an alternatively spliced sirtuin-2 isoform."
Rack J.G., Vanlinden M.R., Lutter T., Aasland R., Ziegler M.
J. Mol. Biol. 426:1677-1691(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION IN DEACETYLATION (ISOFORMS 1 AND 2), ABSENCE OF DEACETYLATION (ISOFORM 5), INTERACTION WITH EP300 (ISOFORMS 1; 2 AND 5), SUBCELLULAR LOCATION (ISOFORMS 1; 2 AND 5).
[5]"Response of autologous T cells to a human melanoma is dominated by individual mutant antigens."
Lennerz V., Fatho M., Gentilini C., Lifke A., Woelfel C., Woelfel T.
Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[6]"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning."
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. expand/collapse author list , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Adrenal gland.
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Lung.
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung.
[10]Mei G., Yu W., Gibbs R.A.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-389 (ISOFORM 4).
Tissue: Brain.
[11]"A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast."
Perrod S., Cockell M.M., Laroche T., Renauld H., Ducrest A.L., Bonnard C., Gasser S.M.
EMBO J. 20:197-209(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[12]"Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening."
Grozinger C.M., Chao E.D., Blackwell H.E., Moazed D., Schreiber S.L.
J. Biol. Chem. 276:38837-38843(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY SIRTINOL; A3 AND M15.
[13]"Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylases."
Borra M.T., O'Neill F.J., Jackson M.D., Marshall B.L., Verdin E., Foltz K.R., Denu J.M.
J. Biol. Chem. 277:12632-12641(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-187.
[14]"The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase."
North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E.
Mol. Cell 11:437-444(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF TUBULIN, SUBCELLULAR LOCATION, INTERACTION WITH HDAC6, MUTAGENESIS OF ASN-168 AND HIS-187.
[15]"Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle."
Dryden S.C., Nahhas F.A., Nowak J.E., Goustin A.-S., Tainsky M.A.
Mol. Cell. Biol. 23:3173-3185(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR OF CELL CYCLE PROGRESSION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PHOSPHORYLATION, UBIQUITINATION, MUTAGENESIS OF HIS-187.
[16]"Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene."
Hiratsuka M., Inoue T., Toda T., Kimura N., Shirayoshi Y., Kamitani H., Watanabe T., Ohama E., Tahimic C.G.T., Kurimasa A., Oshimura M.
Biochem. Biophys. Res. Commun. 309:558-566(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[17]"Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10."
Bae N.S., Swanson M.J., Vassilev A., Howard B.H.
J. Biochem. 135:695-700(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HOXA10.
[18]"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins."
Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.
Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[19]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis."
Vaquero A., Scher M.B., Lee D.H., Sutton A., Cheng H.L., Alt F.W., Serrano L., Sternglanz R., Reinberg D.
Genes Dev. 20:1256-1261(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HISTONE H4 AND H3, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION.
[21]"Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation."
North B.J., Verdin E.
J. Biol. Chem. 282:19546-19555(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR IN CELL CYCLE PROGRESSION, PHOSPHORYLATION AT SER-368 BY CDK1, DEPHOSPHORYLATION AT SER-368 BY CDC14A AND CDC14B, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-187 AND SER-368.
[22]"Mutations in SIRT2 deacetylase which regulate enzymatic activity but not its interaction with HDAC6 and tubulin."
Nahhas F., Dryden S.C., Abrams J., Tainsky M.A.
Mol. Cell. Biochem. 303:221-230(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC6 (ISOFORMS 1 AND 2), PHOSPHORYLATION AT SER-372 AND SER-368, UBIQUITINATION, MUTAGENESIS OF SER-53; SER-98; SER-100; HIS-187; SER-279; THR-280; SER-311; TYR-315; SER-364; SER-368 AND SER-372.
[23]"Mammalian Sir2-related protein (SIRT) 2-mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: a crucial role of tubulin deacetylation."
Suzuki K., Koike T.
Neuroscience 147:599-612(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AXONAL DEGENERATION.
[24]"SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress."
Inoue T., Hiratsuka M., Osaki M., Yamada H., Kishimoto I., Yamaguchi S., Nakano S., Katoh M., Ito H., Oshimura M.
Oncogene 26:945-957(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR OF MITOTIC CELL CYCLE CHECKPOINT, SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, INDUCTION, TISSUE SPECIFICITY, MUTAGENESIS OF GLN-167; ASN-168 AND HIS-187.
[25]"Interphase nucleo-cytoplasmic shuttling and localization of SIRT2 during mitosis."
North B.J., Verdin E.
PLoS ONE 2:E784-E784(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR IN CELL CYCLE PROGRESSION, INTERACTION WITH AURKA, SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING, MUTAGENESIS OF HIS-187.
[26]"Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53."
Jin Y.H., Kim Y.J., Kim D.W., Baek K.H., Kang B.Y., Yeo C.Y., Lee K.Y.
Biochem. Biophys. Res. Commun. 368:690-695(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF TP53, FUNCTION IN REGULATION OF TP53, INTERACTION WITH YWHAB AND YWHAG.
[27]"Acetylation of Sirt2 by p300 attenuates its deacetylase activity."
Han Y., Jin Y.H., Kim Y.J., Kang B.Y., Choi H.J., Kim D.W., Yeo C.Y., Lee K.Y.
Biochem. Biophys. Res. Commun. 375:576-580(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EP300, ACETYLATION BY EP300, ENZYME REGULATION.
[28]"SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells."
Lynn E.G., McLeod C.J., Gordon J.P., Bao J., Sack M.N.
FEBS Lett. 582:2857-2862(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN STRESS RESPONSE, INDUCTION BY STRESS.
[29]"The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility."
Pandithage R., Lilischkis R., Harting K., Wolf A., Jedamzik B., Luscher-Firzlaff J., Vervoorts J., Lasonder E., Kremmer E., Knoll B., Luscher B.
J. Cell Biol. 180:915-929(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF ALPHA-TUBULIN AND HISTONE, FUNCTION IN REGULATION OF CELL MOTILITY, INTERACTION WITH CDK5R1; CDK5 AND CYCLIN E-CDK2 COMPLEX, PHOSPHORYLATION AT SER-368 BY CDK2 AND CDK5, MUTAGENESIS OF SER-368.
[30]"The SIRT2 deacetylase regulates autoacetylation of p300."
Black J.C., Mosley A., Kitada T., Washburn M., Carey M.
Mol. Cell 32:449-455(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF EP300 AND ALPHA-TUBULIN, FUNCTION IN REGULATION OF EP300, SUBCELLULAR LOCATION.
[31]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[32]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[33]"SIRT2 downregulation confers resistance to microtubule inhibitors by prolonging chronic mitotic arrest."
Inoue T., Nakayama Y., Yamada H., Li Y.C., Yamaguchi S., Osaki M., Kurimasa A., Hiratsuka M., Katoh M., Oshimura M.
Cell Cycle 8:1279-1291(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR OF MITOTIC CELL CYCLE CHECKPOINT.
[34]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[35]"p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals."
Vempati R.K., Jayani R.S., Notani D., Sengupta A., Galande S., Haldar D.
J. Biol. Chem. 285:28553-28564(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HISTONE H3.
[36]"SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310."
Rothgiesser K.M., Erener S., Waibel S., Luscher B., Hottiger M.O.
J. Cell Sci. 123:4251-4258(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF RELA, FUNCTION IN REGULATION OF RELA ACTIVITY, INTERACTION WITH RELA, SUBCELLULAR LOCATION.
[37]"Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity."
Zhao Y., Yang J., Liao W., Liu X., Zhang H., Wang S., Wang D., Feng J., Yu L., Zhu W.G.
Nat. Cell Biol. 12:665-675(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN AUTOPHAGY, INTERACTION WITH FOXO1.
[38]"SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity."
Kim H.S., Vassilopoulos A., Wang R.H., Lahusen T., Xiao Z., Xu X., Li C., Veenstra T.D., Li B., Yu H., Ji J., Wang X.W., Park S.H., Cha Y.I., Gius D., Deng C.X.
Cancer Cell 20:487-499(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF CDC20 AND FZR1, FUNCTION AS A TUMOR SUPPRESSOR, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-187.
[39]"The Sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS."
Maxwell M.M., Tomkinson E.M., Nobles J., Wizeman J.W., Amore A.M., Quinti L., Chopra V., Hersch S.M., Kazantsev A.G.
Hum. Mol. Genet. 20:3986-3996(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[40]"Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase."
Jiang W., Wang S., Xiao M., Lin Y., Zhou L., Lei Q., Xiong Y., Guan K.L., Zhao S.
Mol. Cell 43:33-44(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF PCK1, POSSIBLE FUNCTION IN REGULATION OF BLOOD GLUCOSE HOMEOSTASIS, INDUCTION BY GLUCOSE.
[41]"Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling."
Beirowski B., Gustin J., Armour S.M., Yamamoto H., Viader A., North B.J., Michan S., Baloh R.H., Golden J.P., Schmidt R.E., Sinclair D.A., Auwerx J., Milbrandt J.
Proc. Natl. Acad. Sci. U.S.A. 108:E952-961(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF PARD3, INTERACTION WITH PARD3.
[42]"Acetylation regulates subcellular localization of eukaryotic translation initiation factor 5A (eIF5A)."
Ishfaq M., Maeta K., Maeda S., Natsume T., Ito A., Yoshida M.
FEBS Lett. 586:3236-3241(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF EIF5A.
[43]"SIRT2 interferes with autophagy-mediated degradation of protein aggregates in neuronal cells under proteasome inhibition."
Gal J., Bang Y., Choi H.J.
Neurochem. Int. 61:992-1000(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AUTOPHAGY, SUBCELLULAR LOCATION.
[44]"SIRT2 is a tumor suppressor that connects aging, acetylome, cell cycle signaling, and carcinogenesis."
Park S.H., Zhu Y., Ozden O., Kim H.S., Jiang H., Deng C.X., Gius D., Vassilopoulos A.
Transl. Cancer Res. 1:15-21(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW, FUNCTION AS A TUMOR SUPPRESSOR.
[45]"ERK1/2 regulates SIRT2 deacetylase activity."
Choi Y.H., Kim H., Lee S.H., Jin Y.H., Lee K.Y.
Biochem. Biophys. Res. Commun. 437:245-249(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK1/ERK2 AND MAPK3/ERK1.
[46]"The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation."
Serrano L., Martinez-Redondo P., Marazuela-Duque A., Vazquez B.N., Dooley S.J., Voigt P., Beck D.B., Kane-Goldsmith N., Tong Q., Rabanal R.M., Fondevila D., Munoz P., Kruger M., Tischfield J.A., Vaquero A.
Genes Dev. 27:639-653(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HISTONE H4K16 AND SETD8, FUNCTION IN REGULATION OF SETD8 ACTIVITY; H4K20 METHYLATION; CELL CYCLE PROGRESSION AND GENOMIC STABILITY, INTERACTION WITH SETD8, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
[47]"Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth."
Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.
Mol. Cell 51:506-518(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[48]"A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection."
Eskandarian H.A., Impens F., Nahori M.A., Soubigou G., Coppee J.Y., Cossart P., Hamon M.A.
Science 341:1238858-1238858(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HISTONE H3K18, FUNCTION IN LISTERIA INFECTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-168.
[49]"Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis and cell survival during oxidative stress."
Wang Y.P., Zhou L.S., Zhao Y.Z., Wang S.W., Chen L.L., Liu L.X., Ling Z.Q., Hu F.J., Sun Y.P., Zhang J.Y., Yang C., Yang Y., Xiong Y., Guan K.L., Ye D.
EMBO J. 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF G6PD, FUNCTION IN REGULATION OF G6PD ACTIVITY, INTERACTION WITH G6PD, MUTAGENESIS OF ASN-168.
[50]"SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation."
Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., Koh G.Y., Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., Kwak T.H., Kweon G.R.
Oncogene 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF HIF1A, FUNCTION IN REGULATION OF HIF1A STABILITY, INTERACTION WITH HIF1A, MUTAGENESIS OF HIS-187, SUBCELLULAR LOCATION, MASS SPECTROMETRY.
[51]"Structure of the histone deacetylase SIRT2."
Finnin M.S., Donigian J.R., Pavletich N.P.
Nat. Struct. Biol. 8:621-625(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 34-356 IN COMPLEX WITH ZINC, MUTAGENESIS OF ARG-97; GLN-167; ASN-168; ASP-170 AND HIS-187.
[52]"Crystal structure analysis of human Sirt2 and its ADP-ribose complex."
Moniot S., Schutkowski M., Steegborn C.
J. Struct. Biol. 182:136-143(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 34-356 IN COMPLEX WITH NAD ANALOG AND ZINC.
[53]"Structural basis for potent inhibition of SIRT2 deacetylase by a macrocyclic peptide inducing dynamic structural change."
Yamagata K., Goto Y., Nishimasu H., Morimoto J., Ishitani R., Dohmae N., Takeda N., Nagai R., Komuro I., Suga H., Nureki O.
Structure 22:345-352(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.52 ANGSTROMS) OF 55-356 IN COMPLEX WITH PEPTIDE INHIBITOR AND ZINC, ENZYME REGULATION, MUTAGENESIS OF GLU-116; GLU-120; PHE-244; GLN-265; SER-271 AND ASP-294.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF083107 mRNA. Translation: AAD40850.2.
AF095714 mRNA. Translation: AAD45971.1. Different initiation.
AY030277 mRNA. Translation: AAK51133.1.
KF032391 mRNA. Translation: AGZ02589.1.
AJ505014 mRNA. Translation: CAD43717.1.
AF160214 mRNA. Translation: AAF67015.1. Frameshift.
AK290716 mRNA. Translation: BAF83405.1.
AK314492 mRNA. Translation: BAG37092.1.
CH471126 Genomic DNA. Translation: EAW56833.1.
CH471126 Genomic DNA. Translation: EAW56835.1.
BC003012 mRNA. Translation: AAH03012.1.
BC003547 mRNA. Translation: AAH03547.1.
AF131800 mRNA. Translation: AAD20046.1.
CCDSCCDS12523.1. [Q8IXJ6-1]
CCDS46069.1. [Q8IXJ6-2]
RefSeqNP_001180215.1. NM_001193286.1.
NP_036369.2. NM_012237.3. [Q8IXJ6-1]
NP_085096.1. NM_030593.2. [Q8IXJ6-2]
XP_006723174.1. XM_006723111.1. [Q8IXJ6-2]
UniGeneHs.466693.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1J8FX-ray1.70A/B/C34-356[»]
3ZGOX-ray1.63A/B/C34-356[»]
3ZGVX-ray2.27A/B34-356[»]
4L3OX-ray2.52A/B/C/D55-356[»]
ProteinModelPortalQ8IXJ6.
SMRQ8IXJ6. Positions 54-356.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116593. 93 interactions.
DIPDIP-33350N.
IntActQ8IXJ6. 14 interactions.
MINTMINT-3037896.
STRING9606.ENSP00000249396.

Chemistry

BindingDBQ8IXJ6.
ChEMBLCHEMBL4462.

PTM databases

PhosphoSiteQ8IXJ6.

Polymorphism databases

DMDM38258608.

Proteomic databases

MaxQBQ8IXJ6.
PaxDbQ8IXJ6.
PRIDEQ8IXJ6.

Protocols and materials databases

DNASU22933.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000249396; ENSP00000249396; ENSG00000068903. [Q8IXJ6-1]
ENST00000358931; ENSP00000351809; ENSG00000068903. [Q8IXJ6-4]
ENST00000392081; ENSP00000375931; ENSG00000068903. [Q8IXJ6-2]
GeneID22933.
KEGGhsa:22933.
UCSCuc002ojs.2. human. [Q8IXJ6-3]
uc002ojt.2. human. [Q8IXJ6-1]
uc010egh.2. human. [Q8IXJ6-4]

Organism-specific databases

CTD22933.
GeneCardsGC19M039369.
HGNCHGNC:10886. SIRT2.
HPACAB004573.
HPA011165.
MIM604480. gene.
neXtProtNX_Q8IXJ6.
PharmGKBPA35786.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0846.
HOVERGENHBG057095.
KOK11412.
OMATICHYFM.
OrthoDBEOG7WX09C.
PhylomeDBQ8IXJ6.
TreeFamTF106181.

Enzyme and pathway databases

SABIO-RKQ8IXJ6.

Gene expression databases

ArrayExpressQ8IXJ6.
BgeeQ8IXJ6.
CleanExHS_SIRT2.
GenevestigatorQ8IXJ6.

Family and domain databases

Gene3D3.40.50.1220. 2 hits.
InterProIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFPIRSF037938. SIR2_euk. 1 hit.
SUPFAMSSF52467. SSF52467. 1 hit.
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSIRT2. human.
EvolutionaryTraceQ8IXJ6.
GeneWikiSIRT2.
GenomeRNAi22933.
NextBio43669.
PROQ8IXJ6.
SOURCESearch...

Entry information

Entry nameSIR2_HUMAN
AccessionPrimary (citable) accession number: Q8IXJ6
Secondary accession number(s): A8K3V1 expand/collapse secondary AC list , B2RB45, O95889, Q924Y7, Q9P0G8, Q9UNT0, Q9Y6E9, U5TP13
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM