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Q8IXJ6

- SIR2_HUMAN

UniProt

Q8IXJ6 - SIR2_HUMAN

Protein

NAD-dependent protein deacetylase sirtuin-2

Gene

SIRT2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 136 (01 Oct 2014)
      Sequence version 2 (31 Oct 2003)
      Previous versions | rss
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    Functioni

    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.

    Catalytic activityi

    NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.2 PublicationsPROSITE-ProRule annotation

    Cofactori

    Binds 1 zinc ion per subunit.

    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.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei187 – 1871Proton acceptor
    Metal bindingi195 – 1951Zinc3 PublicationsPROSITE-ProRule annotation
    Metal bindingi200 – 2001Zinc3 PublicationsPROSITE-ProRule annotation
    Metal bindingi221 – 2211Zinc3 PublicationsPROSITE-ProRule annotation
    Metal bindingi224 – 2241Zinc3 PublicationsPROSITE-ProRule annotation
    Binding sitei324 – 3241NAD; via amide nitrogen

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi84 – 10421NADAdd
    BLAST
    Nucleotide bindingi167 – 1704NAD
    Nucleotide bindingi261 – 2633NAD
    Nucleotide bindingi286 – 2883NAD

    GO - Molecular functioni

    1. chromatin binding Source: UniProtKB
    2. histone acetyltransferase binding Source: UniProtKB
    3. histone deacetylase activity Source: UniProtKB
    4. histone deacetylase binding Source: UniProtKB
    5. NAD+ binding Source: UniProtKB
    6. NAD-dependent histone deacetylase activity Source: UniProtKB
    7. NAD-dependent histone deacetylase activity (H4-K16 specific) Source: UniProtKB
    8. NAD-dependent protein deacetylase activity Source: UniProtKB
    9. protein binding Source: IntAct
    10. protein deacetylase activity Source: UniProtKB
    11. transcription factor binding Source: UniProtKB
    12. tubulin deacetylase activity Source: UniProtKB
    13. ubiquitin binding Source: UniProtKB
    14. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. autophagy Source: UniProtKB-KW
    2. cell death Source: UniProtKB-KW
    3. cellular lipid catabolic process Source: UniProtKB
    4. cellular response to caloric restriction Source: UniProtKB
    5. cellular response to epinephrine stimulus Source: UniProtKB
    6. cellular response to hepatocyte growth factor stimulus Source: UniProtKB
    7. cellular response to hypoxia Source: UniProtKB
    8. cellular response to molecule of bacterial origin Source: UniProtKB
    9. cellular response to oxidative stress Source: UniProtKB
    10. chromatin silencing Source: UniProtKB
    11. chromatin silencing at rDNA Source: UniProtKB
    12. chromatin silencing at telomere Source: UniProtKB
    13. gene silencing Source: UniProtKB
    14. hepatocyte growth factor receptor signaling pathway Source: UniProtKB
    15. histone deacetylation Source: UniProtKB
    16. histone H3 deacetylation Source: UniProtKB
    17. histone H4 deacetylation Source: UniProtKB
    18. innate immune response Source: UniProtKB-KW
    19. meiotic nuclear division Source: UniProtKB-KW
    20. mitotic nuclear division Source: UniProtKB-KW
    21. myelination in peripheral nervous system Source: UniProtKB
    22. negative regulation of autophagy Source: UniProtKB
    23. negative regulation of cell proliferation Source: UniProtKB
    24. negative regulation of defense response to bacterium Source: UniProtKB
    25. negative regulation of fat cell differentiation Source: UniProtKB
    26. negative regulation of oligodendrocyte progenitor proliferation Source: UniProtKB
    27. negative regulation of peptidyl-threonine phosphorylation Source: UniProtKB
    28. negative regulation of protein catabolic process Source: UniProtKB
    29. negative regulation of reactive oxygen species metabolic process Source: UniProtKB
    30. negative regulation of striated muscle tissue development Source: UniProtKB
    31. negative regulation of transcription, DNA-templated Source: UniProtKB
    32. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    33. negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
    34. peptidyl-lysine deacetylation Source: UniProtKB
    35. phosphatidylinositol 3-kinase signaling Source: UniProtKB
    36. positive regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
    37. positive regulation of cell division Source: UniProtKB
    38. positive regulation of DNA binding Source: UniProtKB
    39. positive regulation of execution phase of apoptosis Source: UniProtKB
    40. positive regulation of meiosis Source: UniProtKB
    41. positive regulation of oocyte maturation Source: UniProtKB
    42. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    43. positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia Source: UniProtKB
    44. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    45. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    46. protein ADP-ribosylation Source: UniProtKB
    47. protein deacetylation Source: UniProtKB
    48. protein kinase B signaling Source: UniProtKB
    49. regulation of cell cycle Source: UniProtKB
    50. regulation of exit from mitosis Source: UniProtKB
    51. regulation of myelination Source: UniProtKB
    52. regulation of phosphorylation Source: UniProtKB
    53. response to redox state Source: UniProtKB
    54. substantia nigra development Source: UniProt
    55. transcription, DNA-templated Source: UniProtKB-KW
    56. tubulin deacetylation Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Autophagy, Cell cycle, Cell division, Differentiation, Immunity, Innate immunity, Meiosis, Mitosis, Neurogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Enzyme and pathway databases

    SABIO-RKQ8IXJ6.

    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
    Name:SIRT2
    Synonyms:SIR2L, SIR2L2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:10886. SIRT2.

    Subcellular locationi

    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.By similarity
    Isoform 1 : Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Predominantly localized in the cytoplasmic.
    Isoform 2 : Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Predominantly localized in the cytoplasmic.
    Isoform 5 : Cytoplasm 1 Publication. Nucleus 1 Publication
    Note: Predominantly localized in the nucleus.

    GO - Cellular componenti

    1. centriole Source: UniProtKB
    2. centrosome Source: UniProtKB
    3. chromatin silencing complex Source: UniProtKB
    4. chromosome Source: UniProtKB
    5. cytoplasm Source: UniProtKB
    6. cytosol Source: UniProtKB
    7. glial cell projection Source: UniProtKB
    8. growth cone Source: UniProtKB-SubCell
    9. juxtaparanode region of axon Source: UniProtKB
    10. lateral loop Source: UniProtKB
    11. meiotic spindle Source: UniProtKB
    12. microtubule Source: UniProtKB
    13. midbody Source: UniProtKB
    14. mitotic spindle Source: UniProtKB
    15. myelin sheath Source: UniProtKB
    16. nuclear heterochromatin Source: UniProtKB
    17. nucleus Source: UniProtKB
    18. paranodal junction Source: UniProtKB
    19. paranode region of axon Source: UniProtKB
    20. perikaryon Source: UniProtKB
    21. perinuclear region of cytoplasm Source: UniProtKB
    22. plasma membrane Source: UniProtKB-KW
    23. Schmidt-Lanterman incisure Source: UniProtKB
    24. spindle Source: UniProtKB

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi53 – 531S → A: Reduces deacetylase activity. 1 Publication
    Mutagenesisi97 – 971R → A: No effect on deacetylase activity. 1 Publication
    Mutagenesisi98 – 981S → A: Inhibits deacetylase activity. 1 Publication
    Mutagenesisi100 – 1001S → A: Reduces deacetylase activity. 1 Publication
    Mutagenesisi116 – 1161E → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication
    Mutagenesisi120 – 1201E → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication
    Mutagenesisi167 – 1671Q → 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. 2 Publications
    Mutagenesisi168 – 1681N → 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. 5 Publications
    Mutagenesisi170 – 1701D → A or N: Reduces deacetylase activity. 1 Publication
    Mutagenesisi187 – 1871H → 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. 11 Publications
    Mutagenesisi244 – 2441F → A: Reduces strongly binding for the peptide inhibitor S2iL5. 1 Publication
    Mutagenesisi265 – 2651Q → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication
    Mutagenesisi271 – 2711S → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication
    Mutagenesisi279 – 2791S → A: Reduces deacetylase activity. 1 Publication
    Mutagenesisi280 – 2801T → A: Reduces deacetylase activity. 1 Publication
    Mutagenesisi294 – 2941D → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication
    Mutagenesisi311 – 3111S → A: Reduces deacetylase activity. 1 Publication
    Mutagenesisi315 – 3151Y → A: Reduces deacetylase activity. 1 Publication
    Mutagenesisi364 – 3641S → A: Abolishes CDK2-dependent phosphorylation. 1 Publication
    Mutagenesisi368 – 3681S → 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. 3 Publications
    Mutagenesisi368 – 3681S → D: Abolishes CDK2-dependent phosphorylation. Inhibits interaction with a cyclin E-CDK2 complex. Reduces strongly histone deacetylation activity. 3 Publications
    Mutagenesisi368 – 3681S → E: Abolishes CDK2-dependent phosphorylation. 3 Publications
    Mutagenesisi372 – 3721S → A: Reduces phosphorylation. Does not inhibit interaction with HDAC6, ubiquitination and deacetylase activity. Inhibits deacetylase activity; when associated with A-368. 1 Publication

    Keywords - Diseasei

    Neurodegeneration

    Organism-specific databases

    PharmGKBiPA35786.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 389388NAD-dependent protein deacetylase sirtuin-2PRO_0000110258Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine2 Publications
    Modified residuei368 – 3681Phosphoserine; by CDK2 (in cyclin E-CDK2 complex); by CDK5 (in cyclin p35-CDK5)4 Publications
    Modified residuei372 – 3721Phosphoserine2 Publications

    Post-translational modificationi

    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.4 Publications
    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.2 Publications
    Ubiquitinated.2 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ8IXJ6.
    PaxDbiQ8IXJ6.
    PRIDEiQ8IXJ6.

    PTM databases

    PhosphoSiteiQ8IXJ6.

    Expressioni

    Tissue specificityi

    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.6 Publications

    Developmental stagei

    Peaks during mitosis. After mitosis, it is probably degraded by the 26S proteasome.1 Publication

    Inductioni

    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.3 Publications

    Gene expression databases

    ArrayExpressiQ8IXJ6.
    BgeeiQ8IXJ6.
    CleanExiHS_SIRT2.
    GenevestigatoriQ8IXJ6.

    Organism-specific databases

    HPAiCAB004573.
    HPA011165.

    Interactioni

    Subunit structurei

    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.By similarity17 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDC14BO607292EBI-477232,EBI-970231
    CDC20Q128342EBI-5240785,EBI-367462
    FZR1Q9UM112EBI-5240785,EBI-724997
    KAT2BQ928314EBI-477232,EBI-477430
    RIPK3Q9Y5722EBI-477232,EBI-298250

    Protein-protein interaction databases

    BioGridi116593. 93 interactions.
    DIPiDIP-33350N.
    IntActiQ8IXJ6. 14 interactions.
    MINTiMINT-3037896.
    STRINGi9606.ENSP00000249396.

    Structurei

    Secondary structure

    1
    389
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi35 – 4511
    Beta strandi60 – 634
    Helixi64 – 718
    Beta strandi73 – 753
    Beta strandi79 – 835
    Helixi85 – 873
    Helixi89 – 913
    Beta strandi96 – 983
    Turni99 – 1013
    Helixi105 – 1106
    Helixi115 – 1195
    Helixi121 – 1266
    Helixi129 – 13810
    Beta strandi139 – 1424
    Helixi147 – 15711
    Beta strandi161 – 1666
    Helixi172 – 1754
    Helixi180 – 1823
    Beta strandi183 – 1853
    Beta strandi188 – 1969
    Turni198 – 2003
    Helixi206 – 21510
    Turni222 – 2243
    Beta strandi227 – 2326
    Helixi242 – 2498
    Helixi250 – 2523
    Beta strandi255 – 2628
    Helixi269 – 2757
    Beta strandi282 – 2887
    Helixi295 – 3039
    Beta strandi309 – 3113
    Beta strandi316 – 3227
    Helixi324 – 33512
    Helixi338 – 35518

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ8IXJ6.
    SMRiQ8IXJ6. Positions 54-356.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8IXJ6.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini65 – 340276Deacetylase sirtuin-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni116 – 1205Peptide inhibitor binding
    Regioni232 – 30170Peptide inhibitor bindingAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi41 – 5111Nuclear export signalAdd
    BLAST

    Sequence similaritiesi

    Belongs to the sirtuin family. Class I subfamily.Curated
    Contains 1 deacetylase sirtuin-type domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0846.
    HOVERGENiHBG057095.
    KOiK11412.
    OMAiTICHYFM.
    OrthoDBiEOG7WX09C.
    PhylomeDBiQ8IXJ6.
    TreeFamiTF106181.

    Family and domain databases

    Gene3Di3.40.50.1220. 2 hits.
    InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR017328. Sirtuin_class_I.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view]
    PANTHERiPTHR11085. PTHR11085. 1 hit.
    PfamiPF02146. SIR2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037938. SIR2_euk. 1 hit.
    SUPFAMiSSF52467. SSF52467. 1 hit.
    PROSITEiPS50305. SIRTUIN. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8IXJ6-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MAEPDPSHPL ETQAGKVQEA QDSDSDSEGG AAGGEADMDF LRNLFSQTLS    50
    LGSQKERLLD ELTLEGVARY MQSERCRRVI CLVGAGISTS AGIPDFRSPS 100
    TGLYDNLEKY HLPYPEAIFE ISYFKKHPEP FFALAKELYP GQFKPTICHY 150
    FMRLLKDKGL LLRCYTQNID TLERIAGLEQ EDLVEAHGTF YTSHCVSASC 200
    RHEYPLSWMK EKIFSEVTPK CEDCQSLVKP DIVFFGESLP ARFFSCMQSD 250
    FLKVDLLLVM GTSLQVQPFA SLISKAPLST PRLLINKEKA GQSDPFLGMI 300
    MGLGGGMDFD SKKAYRDVAW LGECDQGCLA LAELLGWKKE LEDLVRREHA 350
    SIDAQSGAGV PNPSTSASPK KSPPPAKDEA RTTEREKPQ 389
    Length:389
    Mass (Da):43,182
    Last modified:October 31, 2003 - v2
    Checksum:iA392442A8F6316F1
    GO
    Isoform 2 (identifier: Q8IXJ6-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-37: Missing.

    Show »
    Length:352
    Mass (Da):39,515
    Checksum:iFFED07DEF9E3416A
    GO
    Isoform 3 (identifier: Q8IXJ6-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-38: MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADM → MPLAECPSCRCLSSFRSV

    Note: No experimental confirmation available.

    Show »
    Length:369
    Mass (Da):41,353
    Checksum:i0805580CAAB59A51
    GO
    Isoform 4 (identifier: Q8IXJ6-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         266-271: VQPFAS → GRGLAG
         272-389: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:271
    Mass (Da):30,379
    Checksum:iFF4641368029BD94
    GO
    Isoform 5 (identifier: Q8IXJ6-5) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:319
    Mass (Da):35,654
    Checksum:i78A23E5456789A9D
    GO

    Sequence cautioni

    The sequence AAF67015.1 differs from that shown. Reason: Frameshift at several positions.
    The sequence AAD45971.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti199 – 1991S → N(PubMed:10931946)Curated
    Sequence conflicti219 – 2191P → L in CAD43717. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 3838MAEPD…GEADM → MPLAECPSCRCLSSFRSV in isoform 3. 1 PublicationVSP_008726Add
    BLAST
    Alternative sequencei1 – 3737Missing in isoform 2. 5 PublicationsVSP_008724Add
    BLAST
    Alternative sequencei6 – 7671PSHPL…QSERC → R in isoform 5. 1 PublicationVSP_055328Add
    BLAST
    Alternative sequencei266 – 2716VQPFAS → GRGLAG in isoform 4. 1 PublicationVSP_008727
    Alternative sequencei272 – 389118Missing in isoform 4. 1 PublicationVSP_008728Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS12523.1. [Q8IXJ6-1]
    CCDS46069.1. [Q8IXJ6-2]
    RefSeqiNP_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]
    UniGeneiHs.466693.

    Genome annotation databases

    EnsembliENST00000249396; ENSP00000249396; ENSG00000068903. [Q8IXJ6-1]
    ENST00000358931; ENSP00000351809; ENSG00000068903. [Q8IXJ6-4]
    ENST00000392081; ENSP00000375931; ENSG00000068903. [Q8IXJ6-2]
    GeneIDi22933.
    KEGGihsa:22933.
    UCSCiuc002ojs.2. human. [Q8IXJ6-3]
    uc002ojt.2. human. [Q8IXJ6-1]
    uc010egh.2. human. [Q8IXJ6-4]

    Polymorphism databases

    DMDMi38258608.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS12523.1. [Q8IXJ6-1 ]
    CCDS46069.1. [Q8IXJ6-2 ]
    RefSeqi NP_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 ]
    UniGenei Hs.466693.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1J8F X-ray 1.70 A/B/C 34-356 [» ]
    3ZGO X-ray 1.63 A/B/C 34-356 [» ]
    3ZGV X-ray 2.27 A/B 34-356 [» ]
    4L3O X-ray 2.52 A/B/C/D 55-356 [» ]
    ProteinModelPortali Q8IXJ6.
    SMRi Q8IXJ6. Positions 54-356.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116593. 93 interactions.
    DIPi DIP-33350N.
    IntActi Q8IXJ6. 14 interactions.
    MINTi MINT-3037896.
    STRINGi 9606.ENSP00000249396.

    Chemistry

    BindingDBi Q8IXJ6.
    ChEMBLi CHEMBL4462.

    PTM databases

    PhosphoSitei Q8IXJ6.

    Polymorphism databases

    DMDMi 38258608.

    Proteomic databases

    MaxQBi Q8IXJ6.
    PaxDbi Q8IXJ6.
    PRIDEi Q8IXJ6.

    Protocols and materials databases

    DNASUi 22933.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000249396 ; ENSP00000249396 ; ENSG00000068903 . [Q8IXJ6-1 ]
    ENST00000358931 ; ENSP00000351809 ; ENSG00000068903 . [Q8IXJ6-4 ]
    ENST00000392081 ; ENSP00000375931 ; ENSG00000068903 . [Q8IXJ6-2 ]
    GeneIDi 22933.
    KEGGi hsa:22933.
    UCSCi uc002ojs.2. human. [Q8IXJ6-3 ]
    uc002ojt.2. human. [Q8IXJ6-1 ]
    uc010egh.2. human. [Q8IXJ6-4 ]

    Organism-specific databases

    CTDi 22933.
    GeneCardsi GC19M039369.
    HGNCi HGNC:10886. SIRT2.
    HPAi CAB004573.
    HPA011165.
    MIMi 604480. gene.
    neXtProti NX_Q8IXJ6.
    PharmGKBi PA35786.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0846.
    HOVERGENi HBG057095.
    KOi K11412.
    OMAi TICHYFM.
    OrthoDBi EOG7WX09C.
    PhylomeDBi Q8IXJ6.
    TreeFami TF106181.

    Enzyme and pathway databases

    SABIO-RK Q8IXJ6.

    Miscellaneous databases

    ChiTaRSi SIRT2. human.
    EvolutionaryTracei Q8IXJ6.
    GeneWikii SIRT2.
    GenomeRNAii 22933.
    NextBioi 43669.
    PROi Q8IXJ6.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8IXJ6.
    Bgeei Q8IXJ6.
    CleanExi HS_SIRT2.
    Genevestigatori Q8IXJ6.

    Family and domain databases

    Gene3Di 3.40.50.1220. 2 hits.
    InterProi IPR029035. DHS-like_NAD/FAD-binding_dom.
    IPR003000. Sirtuin.
    IPR017328. Sirtuin_class_I.
    IPR026590. Ssirtuin_cat_dom.
    [Graphical view ]
    PANTHERi PTHR11085. PTHR11085. 1 hit.
    Pfami PF02146. SIR2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF037938. SIR2_euk. 1 hit.
    SUPFAMi SSF52467. SSF52467. 1 hit.
    PROSITEi PS50305. SIRTUIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.
      , 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. 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. 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. 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. 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. 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. 33:1304-1320(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. 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.

    Entry informationi

    Entry nameiSIR2_HUMAN
    AccessioniPrimary (citable) accession number: Q8IXJ6
    Secondary accession number(s): A8K3V1
    , B2RB45, O95889, Q924Y7, Q9P0G8, Q9UNT0, Q9Y6E9, U5TP13
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2003
    Last sequence update: October 31, 2003
    Last modified: October 1, 2014
    This is version 136 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3