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Q8VDQ8

- SIR2_MOUSE

UniProt

Q8VDQ8 - SIR2_MOUSE

Protein

NAD-dependent protein deacetylase sirtuin-2

Gene

Sirt2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (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 with both chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by 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. 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 alpha-tubulin.
    Isoform 2: Deacetylates alpha-tubulin.
    Isoform 4: Deacetylates alpha-tubulin.

    Catalytic activityi

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

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Enzyme regulationi

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

    Sites

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

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi84 – 10421NADBy similarityAdd
    BLAST
    Nucleotide bindingi167 – 1704NADBy similarity
    Nucleotide bindingi261 – 2633NADBy similarity
    Nucleotide bindingi286 – 2883NADBy similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. autophagy Source: UniProtKB-KW
    2. cellular lipid catabolic process Source: UniProtKB
    3. cellular response to caloric restriction Source: UniProtKB
    4. cellular response to epinephrine stimulus Source: UniProtKB
    5. cellular response to hepatocyte growth factor stimulus Source: UniProtKB
    6. cellular response to hypoxia Source: UniProtKB
    7. cellular response to molecule of bacterial origin Source: UniProtKB
    8. cellular response to oxidative stress Source: UniProtKB
    9. hepatocyte growth factor receptor signaling pathway Source: UniProtKB
    10. histone deacetylation Source: MGI
    11. histone H3 deacetylation Source: UniProtKB
    12. histone H4 deacetylation Source: UniProtKB
    13. meiotic nuclear division Source: UniProtKB-KW
    14. mitotic nuclear division Source: UniProtKB-KW
    15. myelination in peripheral nervous system Source: UniProtKB
    16. negative regulation of autophagy Source: UniProtKB
    17. negative regulation of cell proliferation Source: UniProtKB
    18. negative regulation of defense response to bacterium Source: UniProtKB
    19. negative regulation of fat cell differentiation Source: UniProtKB
    20. negative regulation of NLRP3 inflammasome complex assembly Source: MGI
    21. negative regulation of oligodendrocyte progenitor proliferation Source: UniProtKB
    22. negative regulation of peptidyl-threonine phosphorylation Source: UniProtKB
    23. negative regulation of protein catabolic process Source: UniProtKB
    24. negative regulation of reactive oxygen species metabolic process Source: UniProtKB
    25. negative regulation of striated muscle tissue development Source: UniProtKB
    26. negative regulation of transcription, DNA-templated Source: UniProtKB
    27. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    28. negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
    29. peptidyl-lysine deacetylation Source: UniProtKB
    30. phosphatidylinositol 3-kinase signaling Source: UniProtKB
    31. positive regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
    32. positive regulation of cell division Source: UniProtKB
    33. positive regulation of DNA binding Source: UniProtKB
    34. positive regulation of execution phase of apoptosis Source: UniProtKB
    35. positive regulation of meiosis Source: UniProtKB
    36. positive regulation of oocyte maturation Source: UniProtKB
    37. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    38. positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia Source: UniProtKB
    39. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    40. proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
    41. protein deacetylation Source: UniProtKB
    42. protein kinase B signaling Source: UniProtKB
    43. regulation of cell cycle Source: UniProtKB
    44. regulation of fat cell differentiation Source: MGI
    45. regulation of myelination Source: UniProtKB
    46. ripoptosome assembly involved in necroptotic process Source: MGI
    47. transcription, DNA-templated Source: UniProtKB-KW
    48. tubulin deacetylation Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Autophagy, Cell cycle, Cell division, Differentiation, Meiosis, Mitosis, Neurogenesis, Transcription, Transcription regulation

    Keywords - Ligandi

    Metal-binding, NAD, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    NAD-dependent protein deacetylase sirtuin-2 (EC:3.5.1.-)
    Alternative name(s):
    Regulatory protein SIR2 homolog 2
    SIR2-like protein 2
    Short name:
    mSIR2L2
    Gene namesi
    Name:Sirt2
    Synonyms:Sir2l2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:1927664. Sirt2.

    Subcellular locationi

    Nucleus. Cytoplasm. Cytoplasmperinuclear region. Perikaryon. Cytoplasmcytoskeleton. Cell projection. Cell projectiongrowth cone. Myelin membrane. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeletonspindle. Chromosome. Midbody. Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole By similarity
    Note: Localizes in the cytoplasm during most of the cell cycle except in the G2/M transition and during mitosis, where it is localized in association with chromatin and induces deacetylation of histone at 'Lys-16' (H4K16ac). Colocalizes with CDK1 at centrosome during prophase and splindle fibers during metaphase. Colocalizes with Aurora kinase AURKA in centrioles during early prophase and growing mitotic spindle throughout metaphase. Colocalizes with Aurora kinase AURKB during cytokinesis with the midbody. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Shuttles between the cytoplasm and the nucleus through the CRM1 export pathway. Colocalizes with EP300 in the nucleus. 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. Deacetylates FOXO3 in the cytoplasm. Colocalizes with Aurora kinase AURKA at centrosome. Colocalizes with microtubules. Colocalizes with PLP1 in internodal regions of myelin sheat, at paranodal axoglial junction and Schmidt-Lanterman incisures. Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal neurons. Colocalizes with alpha-tubulin in neuronal growth cone. Colocalizes with SETD8 at mitotic foci. Localizes in the cytoplasm and nucleus of germinal vesicle (GV) stage oocytes. Colocalizes with alpha-tubulin on the meiotic spindle as the oocytes enter into metaphase, and also during meiotic anaphase and telophase, especially with the midbody.By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Disruption phenotypei

    Tissue-specific knockout of SIRT2 in Schwann cells of early postnatal mice leads to a transient delay in myelination, a reduction in the nerve conduction velocity and hyperacetylation of PARD3. The number of dividing Schwann cells in the developing nerve and alpha-tubulin acetylation are normal (PubMed:21949390). Mutant mice embryo grow normally and new born are healthy. Embryonic fibroblasts (MEFs) display reduced cell proliferation capacity, centrosome amplification and mitotic cell death. Nude mice inoculated with immortalized MEFs from mutant mice developed tumors. Adult mutant mice exhibit genomic instability and chromosomal aberrations, such as double-strand breaks (DSBs), with a gender-specific spectrum of tumorigenesis; females develop primarily mammary tumors and males develop tumors in several organs, including the liver, lung, pancreas, stomach, duodenum and prostate. Drastic increases of histone H4K16 acetylation and decreases of both histone methylation (H4K20me1) in metaphasic chromosomes and histone methylations (H4K20me2/3) in late M/early G1 but also throughout all phases of the cell cycle (PubMed:23468428).3 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi187 – 1871H → A: Abolishes deacetylation of FOXO3. Does not inhibit interaction with FOXO3. 2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 389388NAD-dependent protein deacetylase sirtuin-2PRO_0000110259Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei368 – 3681Phosphoserine; by CDK2 (in cyclin E-CDK2 complex); by CDK5 (in cyclin p35-CDK5)By similarity
    Modified residuei372 – 3721PhosphoserineBy similarity

    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 By similarity.By similarity
    Acetylated by EP300; acetylation leads both to the decreased of SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-mediated down-regulation of TP53 transcriptional activity.By similarity
    Ubiquitinated.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ8VDQ8.
    PaxDbiQ8VDQ8.
    PRIDEiQ8VDQ8.

    PTM databases

    PhosphoSiteiQ8VDQ8.

    Expressioni

    Tissue specificityi

    Isoform 1 is weakly expressed in the cortex at postnatal(P) days P1, P3 and P7, and increases progressively between P17 and older adult cortex. Isoform 1 is also expressed in heart, liver and skeletal muscle, weakly expressed in the striatum and spinal cord. Isoform 2 is not expressed in the cortex at P1, P3 and P7, and increases strongly and progressively between P17 and older adult cortex. Isoform 2 is also expressed in the heart, liver, striatum and spinal cord. Isoform 4 is weakly expressed in older adult cortex and spinal cords. Expressed in the cortex. Expressed in postnatal sciatic nerves during myelination and during remyelination after nerve injury. Expressed in neurons, oligodendrocytes, Schwann cells, Purkinje cells and in astrocytes of white matter. Strongly expressed in preadipocytes compared with differentiated adipocytes. Expressed in cerebellar granule cells. Expressed in the inner ear: in the cochlea, expressed in types I and V fibrocytes in the spiral ligament (SL) and slightly in stria vascularis (SV); in the organ of Corti, expressed in some supporting cells; in the crista ampullaris, expressed in spiral ganglion cells; also expressed in the endolymphatic sac (ES) epithelial cells (at protein level). Expressed in the brain, spinal cord, optic nerve and hippocampus. Strongly expressed in 6-8 week-old ovulated meiosis II oocytes and weakly expressed in 45-58 week-old ovulated meiosis II oocytes. Expressed in the cochlea, vestibule and acoustic nerve of the inner ear.8 Publications

    Developmental stagei

    Isoform 1 is expressed in the cortex at 15.5 dpc. Isoform 2 is not detected in the cortex at 15.5 dpc (at protein level).

    Inductioni

    Up-regulated in response to caloric restriction in white and brown adipose tissues. Up-regulated during cold exposure and down-regulated in higher ambient temperature in brown adipose tissue. Up-regulated after beta-adrenergic agonist (isoproterenol) treatment in white adipose tissue (at protein level). Up-regulated in response to caloric restriction in adipose tissue and kidney. Up-regulated in response to oxidative stress. Up-regulated during postnatal sciatic nerve myelination development and axonal regeneration. Down-regulated during preadipocyte differentiation. Down-regulated in Schwann dedifferentiated cells during Wallerian degeneration. Isoform 1 is up-regulated upon differentiation to a neuron-like phenotype.5 Publications

    Gene expression databases

    ArrayExpressiQ8VDQ8.
    BgeeiQ8VDQ8.
    GenevestigatoriQ8VDQ8.

    Interactioni

    Subunit structurei

    Homotrimer. Interacts (via both phosphorylated, unphosphorylated, active or inactive forms) with HDAC6; the interaction is necessary for the complex to interact with alpha-tubulin, suggesting that these proteins belong to a large complex that deacetylates the cytoskeleton. Interacts with 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; 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 (via C-terminus region) with EP300. Interacts with HIF1A. Interacts with a G1/S-specific cyclin E-CDK2 complex By similarity. 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 AURKA, CDC20, CDK5 (p35 form), FOXO3 and FZR1. Isoform 2 and isoform 4 associate with microtubule in primary cortical mature neurons.By similarity5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AURKAO149655EBI-911012,EBI-448680From a different organism.
    Cdc20Q9JJ662EBI-911012,EBI-2551389
    Fzr1Q9R1K52EBI-911012,EBI-5238560

    Protein-protein interaction databases

    BioGridi211070. 20 interactions.
    IntActiQ8VDQ8. 15 interactions.
    MINTiMINT-4134698.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8VDQ8.
    SMRiQ8VDQ8. Positions 54-356.
    ModBaseiSearch...
    MobiDBiSearch...

    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 bindingBy similarity
    Regioni232 – 30170Peptide inhibitor bindingBy similarityAdd
    BLAST

    Motif

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

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG0846.
    GeneTreeiENSGT00740000115546.
    HOGENOMiHOG000085952.
    HOVERGENiHBG057095.
    InParanoidiQ8VDQ8.
    KOiK11412.
    OMAiTICHYFM.
    OrthoDBiEOG7WX09C.
    PhylomeDBiQ8VDQ8.
    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 (4)i

    Sequence statusi: Complete.

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

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8VDQ8-1) [UniParc]FASTAAdd to Basket

    Also known as: SIRT2.1

    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.

    « Hide

    MAEPDPSDPL ETQAGKVQEA QDSDSDTEGG ATGGEAEMDF LRNLFTQTLG    50
    LGSQKERLLD ELTLEGVTRY MQSERCRKVI CLVGAGISTS AGIPDFRSPS 100
    TGLYANLEKY HLPYPEAIFE ISYFKKHPEP FFALAKELYP GQFKPTICHY 150
    FIRLLKEKGL LLRCYTQNID TLERVAGLEP QDLVEAHGTF YTSHCVNTSC 200
    RKEYTMGWMK EKIFSEATPR CEQCQSVVKP DIVFFGENLP SRFFSCMQSD 250
    FSKVDLLIIM GTSLQVQPFA SLISKAPLAT PRLLINKEKT GQTDPFLGMM 300
    MGLGGGMDFD SKKAYRDVAW LGDCDQGCLA LADLLGWKKE LEDLVRREHA 350
    NIDAQSGSQA PNPSTTISPG KSPPPAKEAA RTKEKEEQQ 389
    Length:389
    Mass (Da):43,256
    Last modified:October 31, 2003 - v2
    Checksum:i15F96635445A1BC0
    GO
    Isoform 2 (identifier: Q8VDQ8-2) [UniParc]FASTAAdd to Basket

    Also known as: SIRT2.2

    The sequence of this isoform differs from the canonical sequence as follows:
         2-37: Missing.

    Show »
    Length:353
    Mass (Da):39,685
    Checksum:iD88E8C48C56B3E20
    GO
    Isoform 3 (identifier: Q8VDQ8-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         236-389: Missing.

    Show »
    Length:235
    Mass (Da):26,518
    Checksum:i173FB866BD739EF0
    GO
    Isoform 4 (identifier: Q8VDQ8-4) [UniParc]FASTAAdd to Basket

    Also known as: SIRT2.3

    The sequence of this isoform differs from the canonical sequence as follows:
         6-76: PSDPLETQAGKVQEAQDSDSDTEGGATGGEAEMDFLRNLFTQTLGLGSQKERLLDELTLEGVTRYMQSERC → R

    Note: Gene prediction based on EST data.

    Show »
    Length:319
    Mass (Da):35,678
    Checksum:i506B6C4028EA9A1F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti230 – 2301P → L in AAG32038. (PubMed:11056054)Curated
    Sequence conflicti241 – 2411S → P in AAH21439. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2 – 3736Missing in isoform 2. 1 PublicationVSP_008729Add
    BLAST
    Alternative sequencei6 – 7671PSDPL…QSERC → R in isoform 4. CuratedVSP_055329Add
    BLAST
    Alternative sequencei236 – 389154Missing in isoform 3. 1 PublicationVSP_055330Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF299337 mRNA. Translation: AAG39256.1.
    AF302272
    , AF302265, AF302266, AF302267, AF302268, AF302269, AF302270, AF302271 Genomic DNA. Translation: AAG32038.1.
    AK014042 mRNA. Translation: BAB29128.1.
    KF032392 mRNA. Translation: AGZ02590.1.
    AC171210 Genomic DNA. No translation available.
    BC021439 mRNA. Translation: AAH21439.1.
    CCDSiCCDS21055.1. [Q8VDQ8-1]
    CCDS52165.1. [Q8VDQ8-4]
    RefSeqiNP_001116237.1. NM_001122765.1.
    NP_001116238.1. NM_001122766.1.
    NP_071877.3. NM_022432.4. [Q8VDQ8-1]
    UniGeneiMm.272443.

    Genome annotation databases

    EnsembliENSMUST00000072965; ENSMUSP00000072732; ENSMUSG00000015149. [Q8VDQ8-1]
    ENSMUST00000170068; ENSMUSP00000132783; ENSMUSG00000015149. [Q8VDQ8-4]
    GeneIDi64383.
    KEGGimmu:64383.
    UCSCiuc009fzt.2. mouse. [Q8VDQ8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF299337 mRNA. Translation: AAG39256.1 .
    AF302272
    , AF302265 , AF302266 , AF302267 , AF302268 , AF302269 , AF302270 , AF302271 Genomic DNA. Translation: AAG32038.1 .
    AK014042 mRNA. Translation: BAB29128.1 .
    KF032392 mRNA. Translation: AGZ02590.1 .
    AC171210 Genomic DNA. No translation available.
    BC021439 mRNA. Translation: AAH21439.1 .
    CCDSi CCDS21055.1. [Q8VDQ8-1 ]
    CCDS52165.1. [Q8VDQ8-4 ]
    RefSeqi NP_001116237.1. NM_001122765.1.
    NP_001116238.1. NM_001122766.1.
    NP_071877.3. NM_022432.4. [Q8VDQ8-1 ]
    UniGenei Mm.272443.

    3D structure databases

    ProteinModelPortali Q8VDQ8.
    SMRi Q8VDQ8. Positions 54-356.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 211070. 20 interactions.
    IntActi Q8VDQ8. 15 interactions.
    MINTi MINT-4134698.

    PTM databases

    PhosphoSitei Q8VDQ8.

    Proteomic databases

    MaxQBi Q8VDQ8.
    PaxDbi Q8VDQ8.
    PRIDEi Q8VDQ8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000072965 ; ENSMUSP00000072732 ; ENSMUSG00000015149 . [Q8VDQ8-1 ]
    ENSMUST00000170068 ; ENSMUSP00000132783 ; ENSMUSG00000015149 . [Q8VDQ8-4 ]
    GeneIDi 64383.
    KEGGi mmu:64383.
    UCSCi uc009fzt.2. mouse. [Q8VDQ8-1 ]

    Organism-specific databases

    CTDi 22933.
    MGIi MGI:1927664. Sirt2.

    Phylogenomic databases

    eggNOGi COG0846.
    GeneTreei ENSGT00740000115546.
    HOGENOMi HOG000085952.
    HOVERGENi HBG057095.
    InParanoidi Q8VDQ8.
    KOi K11412.
    OMAi TICHYFM.
    OrthoDBi EOG7WX09C.
    PhylomeDBi Q8VDQ8.
    TreeFami TF106181.

    Miscellaneous databases

    ChiTaRSi SIRT2. mouse.
    NextBioi 320059.
    PROi Q8VDQ8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8VDQ8.
    Bgeei Q8VDQ8.
    Genevestigatori Q8VDQ8.

    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. "Cloning and characterization of two mouse genes with homology to the yeast sir2 gene."
      Yang Y.H., Chen Y.H., Zhang C.Y., Nimmakayalu M.A., Ward D.C., Weissman S.
      Genomics 69:355-369(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
      Strain: 129/Ola.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Strain: C57BL/6J.
      Tissue: Embryo.
    3. "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 3), ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
      Tissue: Brain.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    5. "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 1).
      Tissue: Mammary tumor.
    6. Lubec G., Klug S., Kang S.U., Sunyer B., Chen W.-Q.
      Submitted (JAN-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 43-55; 58-69; 79-125; 137-153; 164-174; 213-253; 276-282 AND 348-371, IDENTIFICATION BY MASS SPECTROMETRY.
      Strain: C57BL/6 and OF1.
      Tissue: Brain and Hippocampus.
    7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic brain.
    8. "SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction."
      Wang F., Nguyen M., Qin F.X., Tong Q.
      Aging Cell 6:505-514(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3 ACTIVITY, INTERACTION WITH FOXO3, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-187, INDUCTION BY CALORIC RESTRICTION AND OXIDATIVE STRESS.
    9. "SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation."
      Jing E., Gesta S., Kahn C.R.
      Cell Metab. 6:105-114(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN INHIBITION OF ADIPOCYTE DIFFERENTIATION, INTERACTION WITH FOXO1, INDUCTION, TISSUE SPECIFICITY.
    10. Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    11. "Microtubule deacetylases, SirT2 and HDAC6, in the nervous system."
      Southwood C.M., Peppi M., Dryden S., Tainsky M.A., Gow A.
      Neurochem. Res. 32:187-195(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    12. "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 DEACETYLATION OF TUBULIN, FUNCTION IN AXONAL DEGENERATION, SUBCELLULAR LOCATION.
    13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    14. Cited for: INTERACTION WITH CDK5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    15. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    16. "SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma."
      Wang F., Tong Q.
      Mol. Biol. Cell 20:801-808(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEACETYLATION OF FOXO1, FUNCTION IN INHIBITION OF ADIPOCYTE DIFFERENTIATION, INTERACTION WITH FOXO1, SUBCELLULAR LOCATION, INDUCTION BY CALORIC RESTRICTION.
    17. "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, POSSIBLE FUNCTION AS A TUMOR SUPPRESSOR, INTERACTION WITH AURKA; CDC20 AND FZR1, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
    18. "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: ALTERNATIVE SPLICING (ISOFORMS 1; 2 AND 4), FUNCTION IN DEACETYLATION OF ALPHA-TUBULIN (ISOFORMS 1; 2 AND 4), ASSOCIATION WITH ALPHA-TUBULIN (ISOFORMS 2 AND 4), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
    19. "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 REGULATION OF PERIPHERAL MYELINATION, CONDITIONAL KNOCKOUT IN SCHWANN CELL, TISSUE SPECIFICITY, INDUCTION.
    20. "Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation."
      Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q.
      Oncogene 31:1546-1557(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEACETYLATION OF FOXO3, FUNCTION IN REGULATION OF FOXO3 ACTIVITY, MUTAGENESIS OF HIS-187.
    21. "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.
    22. "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 AS A TUMOR SUPPRESSOR, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
    23. "Localization of sirtuins in the mouse inner ear."
      Takumida M., Takumida H., Anniko M.
      Acta Oto-Laryngol. 134:331-338(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    24. "Sirt2 functions in spindle organization and chromosome alignment in mouse oocyte meiosis."
      Zhang L., Hou X., Ma R., Moley K., Schedl T., Wang Q.
      FASEB J. 28:1435-1445(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DEACETYLATION OF HISTONE H4 AND ALPHA-TUBULIN, FUNCTION IN OOCYTE MEIOSIS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiSIR2_MOUSE
    AccessioniPrimary (citable) accession number: Q8VDQ8
    Secondary accession number(s): E9PXF5
    , Q9CXS5, Q9EQ18, Q9ERJ9, U5TP50
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2003
    Last sequence update: October 31, 2003
    Last modified: October 1, 2014
    This is version 128 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3