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Q8VDQ8

- SIR2_MOUSE

UniProt

Q8VDQ8 - SIR2_MOUSE

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Protein

NAD-dependent protein deacetylase sirtuin-2

Gene
Sirt2, Sir2l2
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.11 Publications
Isoform 1: Deacetylates alpha-tubulin.11 Publications
Isoform 2: Deacetylates alpha-tubulin.11 Publications
Isoform 4: Deacetylates alpha-tubulin.11 Publications

Catalytic activityi

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

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei187 – 1871Proton acceptor By similarity
Metal bindingi195 – 1951Zinc By similarity
Metal bindingi200 – 2001Zinc By similarity
Metal bindingi221 – 2211Zinc By similarity
Metal bindingi224 – 2241Zinc By similarity
Binding sitei324 – 3241NAD; via amide nitrogen By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi84 – 10421NAD By similarityAdd
BLAST
Nucleotide bindingi167 – 1704NAD By similarity
Nucleotide bindingi261 – 2633NAD By similarity
Nucleotide bindingi286 – 2883NAD By 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. hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides Source: InterPro
  7. NAD+ binding Source: InterPro
  8. NAD-dependent histone deacetylase activity Source: UniProtKB
  9. NAD-dependent histone deacetylase activity (H4-K16 specific) Source: UniProtKB
  10. NAD-dependent protein deacetylase activity Source: UniProtKB
  11. protein binding Source: UniProtKB
  12. protein deacetylase activity Source: UniProtKB
  13. transcription factor binding Source: UniProtKB
  14. tubulin deacetylase activity Source: UniProtKB
  15. ubiquitin binding Source: UniProtKB
  16. zinc ion binding Source: Ensembl

GO - Biological processi

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

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.12 Publications

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. juxtaparanode region of axon Source: UniProtKB
  8. lateral loop Source: UniProtKB
  9. meiotic spindle Source: UniProtKB
  10. microtubule Source: UniProtKB
  11. midbody Source: UniProtKB
  12. mitotic spindle Source: UniProtKB
  13. myelin sheath Source: UniProtKB
  14. nuclear heterochromatin Source: UniProtKB
  15. nucleus Source: UniProtKB
  16. paranodal junction Source: UniProtKB
  17. paranode region of axon Source: UniProtKB
  18. perikaryon Source: UniProtKB
  19. perinuclear region of cytoplasm Source: UniProtKB
  20. Schmidt-Lanterman incisure Source: UniProtKB
  21. spindle Source: UniProtKB
Complete GO annotation...

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 (1 Publication). 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 (1 Publication).2 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 – 11Removed By similarity
Chaini2 – 389388NAD-dependent protein deacetylase sirtuin-2PRO_0000110259Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei368 – 3681Phosphoserine; by CDK2 (in cyclin E-CDK2 complex); by CDK5 (in cyclin p35-CDK5) By similarity
Modified residuei372 – 3721Phosphoserine By 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.
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.5 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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini65 – 340276Deacetylase sirtuin-typeAdd
BLAST

Region

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

Motif

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

Sequence similaritiesi

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 3736Missing in isoform 2. VSP_008729Add
BLAST
Alternative sequencei6 – 7671PSDPL…QSERC → R in isoform 4. VSP_055329Add
BLAST
Alternative sequencei236 – 389154Missing in isoform 3. VSP_055330Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti230 – 2301P → L in AAG32038. 1 Publication
Sequence conflicti241 – 2411S → P in AAH21439. 1 Publication

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]
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 ]
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 ]
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Publicationsi

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  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: September 3, 2014
This is version 127 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

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