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Q8VDQ8 (SIR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

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

EC=3.5.1.-
Alternative name(s):
Regulatory protein SIR2 homolog 2
SIR2-like protein 2
Short name=mSIR2L2
Gene names
Name:Sirt2
Synonyms:Sir2l2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

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

General annotation (Comments)

Function

NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates 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. Ref.8 Ref.9 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24

Isoform 1:Deacetylates alpha-tubulin. Ref.8 Ref.9 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24

Isoform 2:Deacetylates alpha-tubulin. Ref.8 Ref.9 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24

Isoform 4:Deacetylates alpha-tubulin. Ref.8 Ref.9 Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

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

Subunit structure

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. Ref.8 Ref.9 Ref.14 Ref.16 Ref.17

Subcellular location

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. Ref.1 Ref.8 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.17 Ref.18 Ref.22 Ref.23 Ref.24

Tissue specificity

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. Ref.9 Ref.10 Ref.11 Ref.14 Ref.18 Ref.19 Ref.23 Ref.24

Developmental stage

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).

Induction

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. Ref.8 Ref.9 Ref.16 Ref.18 Ref.19

Post-translational modification

Phosphorylated at phosphoserine and phosphothreonine. Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression. Phosphorylated at Ser-368 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Phosphorylated by cyclin A/Cdk2 and p35-Cdk5 complexes and to a lesser extent by the cyclin D3/Cdk4 and cyclin B/Cdk1, in vitro. Dephosphorylated at Ser-368 by CDC14A and CDC14B around early anaphase 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.

Disruption phenotype

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 (Ref.19). 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 (Ref.22). Ref.17 Ref.22

Sequence similarities

Belongs to the sirtuin family. Class I subfamily.

Contains 1 deacetylase sirtuin-type domain.

Ontologies

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

Inferred from mutant phenotype Ref.16. Source: UniProtKB

cellular response to epinephrine stimulus

Inferred from direct assay Ref.16. Source: UniProtKB

cellular response to hepatocyte growth factor stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to molecule of bacterial origin

Inferred from sequence or structural similarity. Source: UniProtKB

hepatocyte growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3 deacetylation

Inferred from mutant phenotype PubMed 23908241. Source: UniProtKB

histone H4 deacetylation

Inferred from mutant phenotype Ref.24. Source: UniProtKB

histone deacetylation

Inferred from genetic interaction PubMed 20562830. Source: MGI

mitotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

myelination in peripheral nervous system

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of defense response to bacterium

Inferred from mutant phenotype PubMed 23908241. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from mutant phenotype Ref.9Ref.16. Source: UniProtKB

negative regulation of oligodendrocyte progenitor proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of peptidyl-threonine phosphorylation

Inferred from mutant phenotype Ref.19. Source: UniProtKB

negative regulation of striated muscle tissue development

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.9Ref.16PubMed 24681946. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-lysine deacetylation

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylinositol 3-kinase signaling

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of attachment of spindle microtubules to kinetochore

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of cell division

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of meiosis

Inferred from mutant phenotype Ref.24. Source: UniProtKB

positive regulation of oocyte maturation

Inferred from mutant phenotype Ref.24. Source: UniProtKB

proteasome-mediated ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein deacetylation

Inferred from direct assay Ref.9. Source: UniProtKB

protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell cycle

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of myelination

Inferred from mutant phenotype Ref.19. Source: UniProtKB

ripoptosome assembly involved in necroptotic process

Inferred from mutant phenotype PubMed 23201684. Source: MGI

tubulin deacetylation

Inferred from mutant phenotype Ref.24. Source: UniProtKB

   Cellular_componentSchmidt-Lanterman incisure

Inferred from direct assay Ref.11. Source: UniProtKB

centriole

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

chromosome

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.8Ref.9Ref.16Ref.24. Source: UniProtKB

glial cell projection

Inferred from sequence or structural similarity. Source: UniProtKB

juxtaparanode region of axon

Inferred from sequence or structural similarity. Source: UniProtKB

lateral loop

Inferred from sequence or structural similarity. Source: UniProtKB

meiotic spindle

Inferred from direct assay Ref.24. Source: UniProtKB

microtubule

Inferred from sequence or structural similarity. Source: UniProtKB

midbody

Inferred from direct assay Ref.24. Source: UniProtKB

mitotic spindle

Inferred from sequence or structural similarity. Source: UniProtKB

myelin sheath

Inferred from direct assay Ref.11. Source: UniProtKB

nuclear heterochromatin

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay Ref.16Ref.24. Source: UniProtKB

paranodal junction

Inferred from direct assay Ref.11. Source: UniProtKB

paranode region of axon

Inferred from sequence or structural similarity. Source: UniProtKB

perikaryon

Inferred from direct assay Ref.11. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.11. Source: UniProtKB

spindle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionNAD+ binding

Inferred from electronic annotation. Source: InterPro

NAD-dependent histone deacetylase activity

Inferred from sequence or structural similarity. Source: UniProtKB

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

Inferred from sequence or structural similarity. Source: UniProtKB

NAD-dependent protein deacetylase activity

Inferred from sequence or structural similarity. Source: UniProtKB

beta-tubulin binding

Inferred from direct assay PubMed 23201684. Source: MGI

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone acetyltransferase binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone deacetylase activity

Inferred from mutant phenotype Ref.24. Source: UniProtKB

histone deacetylase binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.16. Source: UniProtKB

protein deacetylase activity

Inferred from direct assay Ref.9. Source: UniProtKB

transcription factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

tubulin deacetylase activity

Inferred from mutant phenotype Ref.24. Source: UniProtKB

ubiquitin binding

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8VDQ8-1)

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.
Isoform 2 (identifier: Q8VDQ8-2)

Also known as: SIRT2.2;

The sequence of this isoform differs from the canonical sequence as follows:
     2-37: Missing.
Isoform 3 (identifier: Q8VDQ8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     236-389: Missing.
Isoform 4 (identifier: Q8VDQ8-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 389388NAD-dependent protein deacetylase sirtuin-2
PRO_0000110259

Regions

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

Sites

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

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue3681Phosphoserine; by CDK2 (in a cyclin E-CDK2 complex); by CDK5 (in the cyclin p35-CDK5) By similarity
Modified residue3721Phosphoserine By similarity

Natural variations

Alternative sequence2 – 3736Missing in isoform 2.
VSP_008729
Alternative sequence6 – 7671PSDPL…QSERC → R in isoform 4.
VSP_055329
Alternative sequence236 – 389154Missing in isoform 3.
VSP_055330

Experimental info

Mutagenesis1871H → A: Abolishes deacetylation of FOXO3. Does not inhibit interaction with FOXO3. Ref.8 Ref.20
Sequence conflict2301P → L in AAG32038. Ref.1
Sequence conflict2411S → P in AAH21439. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (SIRT2.1) [UniParc].

Last modified October 31, 2003. Version 2.
Checksum: 15F96635445A1BC0

FASTA38943,256
        10         20         30         40         50         60 
MAEPDPSDPL ETQAGKVQEA QDSDSDTEGG ATGGEAEMDF LRNLFTQTLG LGSQKERLLD 

        70         80         90        100        110        120 
ELTLEGVTRY MQSERCRKVI CLVGAGISTS AGIPDFRSPS TGLYANLEKY HLPYPEAIFE 

       130        140        150        160        170        180 
ISYFKKHPEP FFALAKELYP GQFKPTICHY FIRLLKEKGL LLRCYTQNID TLERVAGLEP 

       190        200        210        220        230        240 
QDLVEAHGTF YTSHCVNTSC RKEYTMGWMK EKIFSEATPR CEQCQSVVKP DIVFFGENLP 

       250        260        270        280        290        300 
SRFFSCMQSD FSKVDLLIIM GTSLQVQPFA SLISKAPLAT PRLLINKEKT GQTDPFLGMM 

       310        320        330        340        350        360 
MGLGGGMDFD SKKAYRDVAW LGDCDQGCLA LADLLGWKKE LEDLVRREHA NIDAQSGSQA 

       370        380 
PNPSTTISPG KSPPPAKEAA RTKEKEEQQ 

« Hide

Isoform 2 (SIRT2.2) [UniParc].

Checksum: D88E8C48C56B3E20
Show »

FASTA35339,685
Isoform 3 [UniParc].

Checksum: 173FB866BD739EF0
Show »

FASTA23526,518
Isoform 4 (SIRT2.3) [UniParc].

Checksum: 506B6C4028EA9A1F
Show »

FASTA31935,678

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
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]"Proteolipid protein is required for transport of sirtuin 2 into CNS myelin."
Werner H.B., Kuhlmann K., Shen S., Uecker M., Schardt A., Dimova K., Orfaniotou F., Dhaunchak A., Brinkmann B.G., Mobius W., Guarente L., Casaccia-Bonnefil P., Jahn O., Nave K.A.
J. Neurosci. 27:7717-7730(2007) [PubMed] [Europe PMC] [Abstract]
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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[14]"The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility."
Pandithage R., Lilischkis R., Harting K., Wolf A., Jedamzik B., Luscher-Firzlaff J., Vervoorts J., Lasonder E., Kremmer E., Knoll B., Luscher B.
J. Cell Biol. 180:915-929(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF299337 mRNA. Translation: AAG39256.1.
AF302272 expand/collapse EMBL AC list , 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.
CCDSCCDS21055.1. [Q8VDQ8-1]
RefSeqNP_001116237.1. NM_001122765.1.
NP_001116238.1. NM_001122766.1.
NP_071877.3. NM_022432.4. [Q8VDQ8-1]
UniGeneMm.272443.

3D structure databases

ProteinModelPortalQ8VDQ8.
SMRQ8VDQ8. Positions 54-356.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid211070. 20 interactions.
IntActQ8VDQ8. 15 interactions.
MINTMINT-4134698.

PTM databases

PhosphoSiteQ8VDQ8.

Proteomic databases

MaxQBQ8VDQ8.
PaxDbQ8VDQ8.
PRIDEQ8VDQ8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000072965; ENSMUSP00000072732; ENSMUSG00000015149. [Q8VDQ8-1]
GeneID64383.
KEGGmmu:64383.
UCSCuc009fzt.2. mouse. [Q8VDQ8-1]

Organism-specific databases

CTD22933.
MGIMGI:1927664. Sirt2.

Phylogenomic databases

eggNOGCOG0846.
GeneTreeENSGT00740000115546.
HOGENOMHOG000085952.
HOVERGENHBG057095.
InParanoidQ8VDQ8.
KOK11412.
OMATICHYFM.
OrthoDBEOG7WX09C.
PhylomeDBQ8VDQ8.
TreeFamTF106181.

Gene expression databases

ArrayExpressQ8VDQ8.
BgeeQ8VDQ8.
GenevestigatorQ8VDQ8.

Family and domain databases

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

Other

ChiTaRSSIRT2. mouse.
NextBio320059.
PROQ8VDQ8.
SOURCESearch...

Entry information

Entry nameSIR2_MOUSE
AccessionPrimary (citable) accession number: Q8VDQ8
Secondary accession number(s): E9PXF5 expand/collapse secondary AC list , Q9CXS5, Q9EQ18, Q9ERJ9, U5TP50
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: July 9, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot