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Protein

NAD-dependent protein deacetylase sirtuin-2

Gene

SIRT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor.
Isoform 1: Deacetylates EP300, alpha-tubulin and histone H3 and H4.
Isoform 2: Deacetylates EP300, alpha-tubulin and histone H3 and H4.
Isoform 5: Lacks deacetylation activity.

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation2 Publications

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Enzyme regulationi

Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei187Proton acceptor1
Metal bindingi195ZincPROSITE-ProRule annotation3 Publications1
Metal bindingi200ZincPROSITE-ProRule annotation3 Publications1
Metal bindingi221ZincPROSITE-ProRule annotation3 Publications1
Metal bindingi224ZincPROSITE-ProRule annotation3 Publications1
Binding sitei324NAD; via amide nitrogen1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi84 – 104NADAdd BLAST21
Nucleotide bindingi167 – 170NAD4
Nucleotide bindingi261 – 263NAD3
Nucleotide bindingi286 – 288NAD3

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • histone acetyltransferase binding Source: UniProtKB
  • histone deacetylase activity Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • NAD+ binding Source: UniProtKB
  • NAD-dependent histone deacetylase activity Source: UniProtKB
  • NAD-dependent histone deacetylase activity (H4-K16 specific) Source: UniProtKB
  • NAD-dependent protein deacetylase activity Source: UniProtKB
  • protein deacetylase activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • tubulin deacetylase activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cellular lipid catabolic process Source: UniProtKB
  • cellular response to caloric restriction Source: UniProtKB
  • cellular response to epinephrine stimulus Source: UniProtKB
  • cellular response to hepatocyte growth factor stimulus Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to molecule of bacterial origin Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • chromatin silencing Source: UniProtKB
  • chromatin silencing at rDNA Source: UniProtKB
  • chromatin silencing at telomere Source: UniProtKB
  • gene silencing Source: UniProtKB
  • hepatocyte growth factor receptor signaling pathway Source: UniProtKB
  • histone deacetylation Source: UniProtKB
  • histone H3 deacetylation Source: UniProtKB
  • histone H4 deacetylation Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • meiotic cell cycle Source: UniProtKB-KW
  • mitotic nuclear division Source: UniProtKB-KW
  • myelination in peripheral nervous system Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of defense response to bacterium Source: UniProtKB
  • negative regulation of fat cell differentiation Source: UniProtKB
  • negative regulation of NLRP3 inflammasome complex assembly Source: Ensembl
  • negative regulation of oligodendrocyte progenitor proliferation Source: UniProtKB
  • negative regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  • negative regulation of protein catabolic process Source: UniProtKB
  • negative regulation of reactive oxygen species metabolic process Source: UniProtKB
  • negative regulation of striated muscle tissue development Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: UniProtKB
  • peptidyl-lysine deacetylation Source: UniProtKB
  • phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB
  • positive regulation of DNA binding Source: UniProtKB
  • positive regulation of execution phase of apoptosis Source: UniProtKB
  • positive regulation of meiotic nuclear division Source: UniProtKB
  • positive regulation of oocyte maturation Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process involved in cellular response to hypoxia Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein ADP-ribosylation Source: UniProtKB
  • protein deacetylation Source: UniProtKB
  • protein kinase B signaling Source: UniProtKB
  • regulation of cell cycle Source: UniProtKB
  • regulation of exit from mitosis Source: UniProtKB
  • regulation of myelination Source: UniProtKB
  • regulation of phosphorylation Source: UniProtKB
  • response to redox state Source: UniProtKB
  • ripoptosome assembly involved in necroptotic process Source: Ensembl
  • substantia nigra development Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • tubulin deacetylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

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

Keywords - Ligandi

Metal-binding, NAD, Zinc

Enzyme and pathway databases

SABIO-RKQ8IXJ6.
SIGNORiQ8IXJ6.

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-2 (EC:3.5.1.-)
Alternative name(s):
Regulatory protein SIR2 homolog 2
SIR2-like protein 2
Gene namesi
Name:SIRT2
Synonyms:SIR2L, SIR2L2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:10886. SIRT2.

Subcellular locationi

  • Nucleus
  • Cytoplasmperinuclear region
  • Cytoplasm
  • Cytoplasmcytoskeleton
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole
  • Cytoplasmcytoskeletonspindle
  • Midbody
  • Chromosome
  • Perikaryon By similarity
  • Cell projection By similarity
  • Cell projectiongrowth cone By similarity
  • Myelin membrane By similarity

  • Note: Deacetylates FOXO3 in the cytoplasm. Colocalizes with PLP1 in internodal regions, at paranodal axoglial junction and Schmidt-Lanterman incisures of myelin sheat. Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal neurons. Colocalizes with alpha-tubulin in neuronal growth cone. Localizes in the cytoplasm and nucleus of germinal vesicle (GV) stage oocytes. Colocalizes with alpha-tubulin on the meiotic spindle as the oocytes enter into metaphase, and also during meiotic anaphase and telophase, especially with the midbody. Colocalizes with PARD3 in internodal region of axons. Colocalizes with acetylated alpha-tubulin in cell projection processes during primary oligodendrocyte precursor (OLP) differentiation (By similarity). Localizes in the cytoplasm during most of the cell cycle except in the G2/M transition and during mitosis, where it is localized in association with chromatin and induces deacetylation of histone at 'Lys-16' (H4K16ac). Colocalizes with KMT5A at mitotic foci. Colocalizes with CDK1 at centrosome during prophase and splindle fibers during metaphase. Colocalizes with Aurora kinase AURKA at centrosome during early prophase and in the centrioles and growing mitotic spindle throughout metaphase. Colocalizes with Aurora kinase AURKB during cytokinesis with the midbody. Colocalizes with microtubules. Detected in perinuclear foci that may be aggresomes containing misfolded, ubiquitinated proteins. Shuttles between the cytoplasm and the nucleus through the CRM1 export pathway. Colocalizes with EP300 in the nucleus. Translocates to the nucleus and chromatin upon bacterium Listeria monocytogenes infection in interphase cells.By similarity
Isoform 1 :
  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Predominantly localized in the cytoplasmic.
Isoform 2 :
  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Predominantly localized in the cytoplasmic.
Isoform 5 :
  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Predominantly localized in the nucleus.

GO - Cellular componenti

  • centriole Source: UniProtKB
  • centrosome Source: UniProtKB
  • chromatin silencing complex Source: UniProtKB
  • chromosome Source: UniProtKB
  • chromosome, telomeric region Source: GOC
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • glial cell projection Source: UniProtKB
  • growth cone Source: UniProtKB-SubCell
  • juxtaparanode region of axon Source: UniProtKB
  • lateral loop Source: UniProtKB
  • meiotic spindle Source: UniProtKB
  • microtubule Source: UniProtKB
  • midbody Source: UniProtKB
  • mitotic spindle Source: UniProtKB
  • myelin sheath Source: UniProtKB
  • nuclear heterochromatin Source: UniProtKB
  • nucleus Source: UniProtKB
  • paranodal junction Source: UniProtKB
  • paranode region of axon Source: UniProtKB
  • perikaryon Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB-KW
  • Schmidt-Lanterman incisure Source: UniProtKB
  • spindle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi53S → A: Reduces deacetylase activity. 1 Publication1
Mutagenesisi97R → A: No effect on deacetylase activity. 1 Publication1
Mutagenesisi98S → A: Inhibits deacetylase activity. 1 Publication1
Mutagenesisi100S → A: Reduces deacetylase activity. 1 Publication1
Mutagenesisi116E → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication1
Mutagenesisi120E → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication1
Mutagenesisi167Q → A: Reduces deacetylase activity. Inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell formation in response to mitotic stress; when associated with A-168 and A-187. 2 Publications1
Mutagenesisi168N → A: Abolishes deacetylation of alpha-tubulin. Inhibits deacetylation of histone H3 at 'Lys-18'. Inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell formation in response to mitotic stress; when associated with A-167 and A-187. 5 Publications1
Mutagenesisi170D → A or N: Reduces deacetylase activity. 1 Publication1
Mutagenesisi187H → Y or A: Inhibits histone, alpha-tubulin, FZR1 and CDC20 deacetylation activities. No effect on CDK2-dependent phosphorylation. Does not inhibit interaction with HDAC6, HIF1A and the cyclin E-CDK2 complex. Inhibits interaction with KMT5A. Abolishes deacetylation, dimeric formation and enzymatic activity increase of G6PD. Prevents histone H4 methylation at 'Lys-20'(H4K20me1) in metaphase chromosomes. Inhibits the block of entry to chromosome condensation and subsequent hyperploidy cell formation in response to mitotic stress; when associated with A-167 and A-168. 11 Publications1
Mutagenesisi244F → A: Reduces strongly binding for the peptide inhibitor S2iL5. 1 Publication1
Mutagenesisi265Q → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication1
Mutagenesisi271S → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication1
Mutagenesisi279S → A: Reduces deacetylase activity. 1 Publication1
Mutagenesisi280T → A: Reduces deacetylase activity. 1 Publication1
Mutagenesisi294D → A: Reduces binding for the peptide inhibitor S2iL5. 1 Publication1
Mutagenesisi311S → A: Reduces deacetylase activity. 1 Publication1
Mutagenesisi315Y → A: Reduces deacetylase activity. 1 Publication1
Mutagenesisi364S → A: Abolishes CDK2-dependent phosphorylation. 1 Publication1
Mutagenesisi368S → A: Does not affect deacetylase activity. Abolishes CDK2-dependent phosphorylation. Inhibits cellular proliferation delay in the early metaphase to prevent chromosomal instability. Does not inhibit interaction with a cyclin E-CDK2 complex. Does not inhibit interaction with HDAC6 and ubiquitination. Inhibits cell adhesion and migration and neurite outgrowth. Inhibits deacetylase activity; when associated with A-372. 3 Publications1
Mutagenesisi368S → D: Abolishes CDK2-dependent phosphorylation. Inhibits interaction with a cyclin E-CDK2 complex. Reduces strongly histone deacetylation activity. 3 Publications1
Mutagenesisi368S → E: Abolishes CDK2-dependent phosphorylation. 3 Publications1
Mutagenesisi372S → A: Reduces phosphorylation. Does not inhibit interaction with HDAC6, ubiquitination and deacetylase activity. Inhibits deacetylase activity; when associated with A-368. 1 Publication1

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

DisGeNETi22933.
OpenTargetsiENSG00000068903.
ENSG00000283100.
PharmGKBiPA35786.

Chemistry databases

ChEMBLiCHEMBL4462.
GuidetoPHARMACOLOGYi2708.

Polymorphism and mutation databases

BioMutaiSIRT2.
DMDMi38258608.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001102582 – 389NAD-dependent protein deacetylase sirtuin-2Add BLAST388

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei23PhosphoserineCombined sources1
Modified residuei25PhosphoserineCombined sources1
Modified residuei27PhosphoserineCombined sources1
Modified residuei53PhosphoserineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei207PhosphoserineBy similarity1
Modified residuei368Phosphoserine; by CDK2 (in cyclin E-CDK2 complex); by CDK5 (in cyclin p35-CDK5)Combined sources3 Publications1
Modified residuei372Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated at phosphoserine and phosphothreonine. Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression. Phosphorylated at Ser-368 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Phosphorylated by cyclin A/Cdk2 and p35-Cdk5 complexes and to a lesser extent by the cyclin D3/Cdk4 and cyclin B/Cdk1, in vitro. Dephosphorylated at Ser-368 by CDC14A and CDC14B around early anaphase.4 Publications
Acetylated by EP300; acetylation leads both to the decreased of SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-mediated down-regulation of TP53 transcriptional activity.1 Publication
Ubiquitinated.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8IXJ6.
MaxQBiQ8IXJ6.
PaxDbiQ8IXJ6.
PeptideAtlasiQ8IXJ6.
PRIDEiQ8IXJ6.

PTM databases

iPTMnetiQ8IXJ6.
PhosphoSitePlusiQ8IXJ6.

Expressioni

Tissue specificityi

Isoform 1 is expressed in heart, liver and skeletal muscle, weakly expressed in the cortex. Isoform 2 is strongly expressed in the cortex, weakly expressed in heart and liver. Weakly expressed in several malignancies including breast, liver, brain, kidney and prostate cancers compared to normal tissues. Weakly expressed in glioma cell lines compared to normal brain tissues (at protein level). Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Down-regulated in many gliomas suggesting that it may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network.6 Publications

Developmental stagei

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

Inductioni

Up-regulated in response to low levels of glucose and anoxia-reoxygenation stress. Up-regulated by trichostatin A. Down-regulated in response to high levels of glucose. Down-regulated by histone deacetylation in several tumors.3 Publications

Gene expression databases

BgeeiENSG00000068903.
CleanExiHS_SIRT2.
ExpressionAtlasiQ8IXJ6. baseline and differential.
GenevisibleiQ8IXJ6. HS.

Organism-specific databases

HPAiCAB004573.
HPA011165.

Interactioni

Subunit structurei

Interacts with CDC20, FOXO3 and FZR1. Associates with microtubule in primary cortical mature neurons (By similarity). Homotrimer. Isoform 1 and isoform 2 interact (via both phosphorylated, unphosphorylated, active or inactive forms) with HDAC6; the interaction is necessary for the complex to interact with alpha-tubulin, suggesting that these proteins belong to a large complex that deacetylates the cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon serum-starvation or oxidative stress, leading to increased level of acetylated FOXO1 and induction of autophagy. Interacts with RELA; the interaction occurs in the cytoplasm and is increased in a TNF-alpha-dependent manner. Interacts with HOXA10; the interaction is direct. Interacts with YWHAB and YWHAG; the interactions occur in a AKT-dependent manner and increase SIRT2-dependent TP53 deacetylation. Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions increase SIRT2 stability and deacetylation activity. Interacts (phosphorylated form) with KMT5A isoform 2; the interaction is direct, stimulates KMT5A-mediated methyltransferase activity on histone at 'Lys-20' (H4K20me1) and is increased in a H2O(2)-induced oxidative stress-dependent manner. Interacts with G6PD; the interaction is enhanced by H2O2 treatment. Interacts with a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A. Isoform 1, isoform 2 and isoform 5 interact (via C-terminus region) with EP300.By similarity17 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BUB1BO605663EBI-477232,EBI-1001438
CDC14BO607292EBI-477232,EBI-970231
CDC20Q128342EBI-5240785,EBI-367462
FZR1Q9UM112EBI-5240785,EBI-724997
G6PDP114133EBI-477232,EBI-4289891
KAT2BQ928314EBI-477232,EBI-477430
RELAQ042062EBI-477232,EBI-73886
RIPK3Q9Y5722EBI-477232,EBI-298250

GO - Molecular functioni

  • histone acetyltransferase binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116593. 59 interactors.
DIPiDIP-33350N.
IntActiQ8IXJ6. 28 interactors.
MINTiMINT-3037896.
STRINGi9606.ENSP00000249396.

Chemistry databases

BindingDBiQ8IXJ6.

Structurei

Secondary structure

1389
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 45Combined sources11
Beta strandi60 – 63Combined sources4
Helixi64 – 71Combined sources8
Beta strandi73 – 75Combined sources3
Beta strandi79 – 83Combined sources5
Helixi85 – 87Combined sources3
Helixi89 – 91Combined sources3
Beta strandi96 – 98Combined sources3
Helixi99 – 101Combined sources3
Helixi103 – 105Combined sources3
Helixi108 – 110Combined sources3
Helixi115 – 119Combined sources5
Helixi121 – 126Combined sources6
Helixi129 – 138Combined sources10
Beta strandi139 – 142Combined sources4
Helixi147 – 157Combined sources11
Beta strandi161 – 166Combined sources6
Helixi172 – 175Combined sources4
Helixi180 – 182Combined sources3
Beta strandi183 – 185Combined sources3
Beta strandi188 – 196Combined sources9
Turni198 – 200Combined sources3
Beta strandi203 – 205Combined sources3
Helixi206 – 215Combined sources10
Turni222 – 224Combined sources3
Beta strandi227 – 232Combined sources6
Helixi241 – 250Combined sources10
Turni251 – 253Combined sources3
Beta strandi255 – 261Combined sources7
Helixi269 – 275Combined sources7
Beta strandi282 – 288Combined sources7
Turni295 – 297Combined sources3
Helixi301 – 303Combined sources3
Beta strandi309 – 311Combined sources3
Beta strandi316 – 322Combined sources7
Helixi324 – 334Combined sources11
Helixi338 – 353Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J8FX-ray1.70A/B/C34-356[»]
3ZGOX-ray1.63A/B/C34-356[»]
3ZGVX-ray2.27A/B34-356[»]
4L3OX-ray2.52A/B/C/D55-356[»]
4R8MX-ray2.10A/B38-356[»]
4RMGX-ray1.88A56-356[»]
4RMHX-ray1.42A56-356[»]
4RMIX-ray1.45A56-356[»]
4RMJX-ray1.87A/B56-356[»]
4X3OX-ray1.50A52-355[»]
4X3PX-ray1.80A52-355[»]
4Y6LX-ray1.60A/B52-356[»]
4Y6OX-ray1.60A/B52-356[»]
4Y6QX-ray1.90A/B/C/D52-356[»]
5D7OX-ray1.63A/B50-356[»]
5D7PX-ray1.76A/B56-356[»]
5D7QX-ray2.01A/B56-356[»]
5DY4X-ray1.77A56-356[»]
5DY5X-ray1.95A56-356[»]
5FYQX-ray3.00A/B1-356[»]
ProteinModelPortaliQ8IXJ6.
SMRiQ8IXJ6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IXJ6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 340Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST276

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni116 – 120Peptide inhibitor binding5
Regioni232 – 301Peptide inhibitor bindingAdd BLAST70

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi41 – 51Nuclear export signalAdd BLAST11

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2682. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132288.
HOVERGENiHBG057095.
InParanoidiQ8IXJ6.
KOiK11412.
PhylomeDBiQ8IXJ6.
TreeFamiTF106181.

Family and domain databases

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

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

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

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MAEPDPSHPL ETQAGKVQEA QDSDSDSEGG AAGGEADMDF LRNLFSQTLS
60 70 80 90 100
LGSQKERLLD ELTLEGVARY MQSERCRRVI CLVGAGISTS AGIPDFRSPS
110 120 130 140 150
TGLYDNLEKY HLPYPEAIFE ISYFKKHPEP FFALAKELYP GQFKPTICHY
160 170 180 190 200
FMRLLKDKGL LLRCYTQNID TLERIAGLEQ EDLVEAHGTF YTSHCVSASC
210 220 230 240 250
RHEYPLSWMK EKIFSEVTPK CEDCQSLVKP DIVFFGESLP ARFFSCMQSD
260 270 280 290 300
FLKVDLLLVM GTSLQVQPFA SLISKAPLST PRLLINKEKA GQSDPFLGMI
310 320 330 340 350
MGLGGGMDFD SKKAYRDVAW LGECDQGCLA LAELLGWKKE LEDLVRREHA
360 370 380
SIDAQSGAGV PNPSTSASPK KSPPPAKDEA RTTEREKPQ
Length:389
Mass (Da):43,182
Last modified:October 31, 2003 - v2
Checksum:iA392442A8F6316F1
GO
Isoform 2 (identifier: Q8IXJ6-2) [UniParc]FASTAAdd to basket

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

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

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

Note: No experimental confirmation available.
Show »
Length:369
Mass (Da):41,353
Checksum:i0805580CAAB59A51
GO
Isoform 4 (identifier: Q8IXJ6-4) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:271
Mass (Da):30,379
Checksum:iFF4641368029BD94
GO
Isoform 5 (identifier: Q8IXJ6-5) [UniParc]FASTAAdd to basket

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

Note: Lacks deacetylase activity, at least toward known SIRT2 targets.
Show »
Length:319
Mass (Da):35,654
Checksum:i78A23E5456789A9D
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti199S → N (PubMed:10931946).Curated1
Sequence conflicti219P → L in CAD43717 (Ref. 5) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0087261 – 38MAEPD…GEADM → MPLAECPSCRCLSSFRSV in isoform 3. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_0087241 – 37Missing in isoform 2. 5 PublicationsAdd BLAST37
Alternative sequenceiVSP_0553286 – 76PSHPL…QSERC → R in isoform 5. 1 PublicationAdd BLAST71
Alternative sequenceiVSP_008727266 – 271VQPFAS → GRGLAG in isoform 4. 1 Publication6
Alternative sequenceiVSP_008728272 – 389Missing in isoform 4. 1 PublicationAdd BLAST118

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF083107 mRNA. Translation: AAD40850.2.
AF095714 mRNA. Translation: AAD45971.1. Different initiation.
AY030277 mRNA. Translation: AAK51133.1.
KF032391 mRNA. Translation: AGZ02589.1.
AJ505014 mRNA. Translation: CAD43717.1.
AF160214 mRNA. Translation: AAF67015.1. Frameshift.
AK290716 mRNA. Translation: BAF83405.1.
AK314492 mRNA. Translation: BAG37092.1.
CH471126 Genomic DNA. Translation: EAW56833.1.
CH471126 Genomic DNA. Translation: EAW56835.1.
BC003012 mRNA. Translation: AAH03012.1.
BC003547 mRNA. Translation: AAH03547.1.
AF131800 mRNA. Translation: AAD20046.1.
CCDSiCCDS12523.1. [Q8IXJ6-1]
CCDS46069.1. [Q8IXJ6-2]
RefSeqiNP_001180215.1. NM_001193286.1.
NP_036369.2. NM_012237.3. [Q8IXJ6-1]
NP_085096.1. NM_030593.2. [Q8IXJ6-2]
XP_006723174.1. XM_006723111.1. [Q8IXJ6-2]
XP_011524956.1. XM_011526654.1. [Q8IXJ6-2]
XP_011524957.1. XM_011526655.1. [Q8IXJ6-5]
UniGeneiHs.466693.

Genome annotation databases

EnsembliENST00000249396; ENSP00000249396; ENSG00000068903. [Q8IXJ6-1]
ENST00000392081; ENSP00000375931; ENSG00000068903. [Q8IXJ6-2]
ENST00000634533; ENSP00000489602; ENSG00000283100. [Q8IXJ6-1]
ENST00000635478; ENSP00000488940; ENSG00000283100. [Q8IXJ6-2]
GeneIDi22933.
KEGGihsa:22933.
UCSCiuc002ojt.3. human. [Q8IXJ6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF083107 mRNA. Translation: AAD40850.2.
AF095714 mRNA. Translation: AAD45971.1. Different initiation.
AY030277 mRNA. Translation: AAK51133.1.
KF032391 mRNA. Translation: AGZ02589.1.
AJ505014 mRNA. Translation: CAD43717.1.
AF160214 mRNA. Translation: AAF67015.1. Frameshift.
AK290716 mRNA. Translation: BAF83405.1.
AK314492 mRNA. Translation: BAG37092.1.
CH471126 Genomic DNA. Translation: EAW56833.1.
CH471126 Genomic DNA. Translation: EAW56835.1.
BC003012 mRNA. Translation: AAH03012.1.
BC003547 mRNA. Translation: AAH03547.1.
AF131800 mRNA. Translation: AAD20046.1.
CCDSiCCDS12523.1. [Q8IXJ6-1]
CCDS46069.1. [Q8IXJ6-2]
RefSeqiNP_001180215.1. NM_001193286.1.
NP_036369.2. NM_012237.3. [Q8IXJ6-1]
NP_085096.1. NM_030593.2. [Q8IXJ6-2]
XP_006723174.1. XM_006723111.1. [Q8IXJ6-2]
XP_011524956.1. XM_011526654.1. [Q8IXJ6-2]
XP_011524957.1. XM_011526655.1. [Q8IXJ6-5]
UniGeneiHs.466693.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J8FX-ray1.70A/B/C34-356[»]
3ZGOX-ray1.63A/B/C34-356[»]
3ZGVX-ray2.27A/B34-356[»]
4L3OX-ray2.52A/B/C/D55-356[»]
4R8MX-ray2.10A/B38-356[»]
4RMGX-ray1.88A56-356[»]
4RMHX-ray1.42A56-356[»]
4RMIX-ray1.45A56-356[»]
4RMJX-ray1.87A/B56-356[»]
4X3OX-ray1.50A52-355[»]
4X3PX-ray1.80A52-355[»]
4Y6LX-ray1.60A/B52-356[»]
4Y6OX-ray1.60A/B52-356[»]
4Y6QX-ray1.90A/B/C/D52-356[»]
5D7OX-ray1.63A/B50-356[»]
5D7PX-ray1.76A/B56-356[»]
5D7QX-ray2.01A/B56-356[»]
5DY4X-ray1.77A56-356[»]
5DY5X-ray1.95A56-356[»]
5FYQX-ray3.00A/B1-356[»]
ProteinModelPortaliQ8IXJ6.
SMRiQ8IXJ6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116593. 59 interactors.
DIPiDIP-33350N.
IntActiQ8IXJ6. 28 interactors.
MINTiMINT-3037896.
STRINGi9606.ENSP00000249396.

Chemistry databases

BindingDBiQ8IXJ6.
ChEMBLiCHEMBL4462.
GuidetoPHARMACOLOGYi2708.

PTM databases

iPTMnetiQ8IXJ6.
PhosphoSitePlusiQ8IXJ6.

Polymorphism and mutation databases

BioMutaiSIRT2.
DMDMi38258608.

Proteomic databases

EPDiQ8IXJ6.
MaxQBiQ8IXJ6.
PaxDbiQ8IXJ6.
PeptideAtlasiQ8IXJ6.
PRIDEiQ8IXJ6.

Protocols and materials databases

DNASUi22933.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000249396; ENSP00000249396; ENSG00000068903. [Q8IXJ6-1]
ENST00000392081; ENSP00000375931; ENSG00000068903. [Q8IXJ6-2]
ENST00000634533; ENSP00000489602; ENSG00000283100. [Q8IXJ6-1]
ENST00000635478; ENSP00000488940; ENSG00000283100. [Q8IXJ6-2]
GeneIDi22933.
KEGGihsa:22933.
UCSCiuc002ojt.3. human. [Q8IXJ6-1]

Organism-specific databases

CTDi22933.
DisGeNETi22933.
GeneCardsiSIRT2.
HGNCiHGNC:10886. SIRT2.
HPAiCAB004573.
HPA011165.
MIMi604480. gene.
neXtProtiNX_Q8IXJ6.
OpenTargetsiENSG00000068903.
ENSG00000283100.
PharmGKBiPA35786.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2682. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00850000132288.
HOVERGENiHBG057095.
InParanoidiQ8IXJ6.
KOiK11412.
PhylomeDBiQ8IXJ6.
TreeFamiTF106181.

Enzyme and pathway databases

SABIO-RKQ8IXJ6.
SIGNORiQ8IXJ6.

Miscellaneous databases

ChiTaRSiSIRT2. human.
EvolutionaryTraceiQ8IXJ6.
GeneWikiiSIRT2.
GenomeRNAii22933.
PROiQ8IXJ6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000068903.
CleanExiHS_SIRT2.
ExpressionAtlasiQ8IXJ6. baseline and differential.
GenevisibleiQ8IXJ6. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiSIR2_HUMAN
AccessioniPrimary (citable) accession number: Q8IXJ6
Secondary accession number(s): A8K3V1
, B2RB45, O95889, Q924Y7, Q9P0G8, Q9UNT0, Q9Y6E9, U5TP13
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: November 2, 2016
This is version 160 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.