DEPOD - human DEPhOsphorylation Database

Basic Information
Phosphatases
Pathway
Interacting Proteins
Phosphorylating Kinases

Gene Name	SIRT2 (QuickGO)	Interactive visualization of SIRT2 structures (A quick tutorial to explore the interctive visulaization) Representative structure: 5DY4
Synonyms	SIRT2, SIR2L, SIR2L2
Protein Name	SIRT2
Alternative Name(s)	NAD-dependent protein deacetylase sirtuin-2;3.5.1.-;Regulatory protein SIR2 homolog 2;SIR2-like protein 2;
Protein Family	Belongs to the sirtuin family Class I subfamily
EntrezGene ID	22933 (Comparitive Toxicogenomics)
UniProt AC (Human)	Q8IXJ6 (protein sequence)
Enzyme Class	N/A
Molecular Weight	43182 Dalton
Protein Length	389 amino acids (AA)
Genome Browsers	NCBI \| ENSG00000068903 (Ensembl) \| ENSG00000283100 (Ensembl) \| UCSC
Crosslinking annotations	Query our ID-mapping table
Orthologues	Quest For Orthologues (QFO) \| GeneTree \| eggNOG - KOG2682 \| eggNOG - COG0846
Phosphorylation Network	Visualize

Domain organization, Expression, Diseases

(show / hide)

Localization, Function, Catalytic activity and Sequence

(show / hide)

Localization (UniProt annotation)
Nucleus Cytoplasm, perinuclear regionCytoplasm Cytoplasm, cytoskeleton Cytoplasm, cytoskeleton,microtubule organizing center, centrosome Cytoplasm,cytoskeleton, microtubule organizing center, centrosome,centriole Cytoplasm, cytoskeleton, spindle Midbody ChromosomePerikaryon Cell projection Cellprojection, growth cone Myelin membrane Note=Deacetylates FOXO3 in the cytoplasmColocalizes with PLP1 in internodal regions, at paranodal axoglialjunction and Schmidt-Lanterman incisures of myelin sheatColocalizes with CDK5R1 in the perikaryon, neurites and growthcone of hippocampal neurons Colocalizes with alpha-tubulin inneuronal growth cone Localizes in the cytoplasm and nucleus ofgerminal vesicle (GV) stage oocytes Colocalizes with alpha-tubulin on the meiotic spindle as the oocytes enter intometaphase, and also during meiotic anaphase and telophase,especially with the midbody Colocalizes with PARD3 in internodalregion of axons Colocalizes with acetylated alpha-tubulin in cellprojection processes during primary oligodendrocyte precursor(OLP) differentiation (By similarity) Localizes in the cytoplasmduring most of the cell cycle except in the G2/M transition andduring mitosis, where it is localized in association withchromatin and induces deacetylation of histone at 'Lys-16'(H4K16ac) Colocalizes with KMT5A at mitotic foci Colocalizeswith CDK1 at centrosome during prophase and splindle fibers duringmetaphase Colocalizes with Aurora kinase AURKA at centrosomeduring early prophase and in the centrioles and growing mitoticspindle throughout metaphase Colocalizes with Aurora kinase AURKBduring cytokinesis with the midbody Colocalizes withmicrotubules Detected in perinuclear foci that may be aggresomescontaining misfolded, ubiquitinated proteins Shuttles between thecytoplasm and the nucleus through the CRM1 export pathwayColocalizes with EP300 in the nucleus Translocates to the nucleusand chromatin upon bacterium Listeria monocytogenes infection ininterphase cells Isoform 1: Cytoplasm Nucleus Note=Predominantly localized in thecytoplasmic Isoform 2: Cytoplasm Nucleus Note=Predominantly localized in thecytoplasmic Isoform 5: Cytoplasm Nucleus Note=Predominantly localized in thenucleus
Function (UniProt annotation)
NAD-dependent protein deacetylase, which deacetylatesinternal lysines on histone and alpha-tubulin as well as manyother proteins such as key transcription factors (PubMed:24177535,PubMed:12620231, PubMed:16648462, PubMed:18249187,PubMed:18332217, PubMed:18995842, PubMed:20587414,PubMed:21081649, PubMed:20543840, PubMed:22014574,PubMed:21726808, PubMed:21949390, PubMed:22771473,PubMed:23468428, PubMed:23908241, PubMed:24940000,PubMed:24769394, PubMed:24681946) Participates in the modulationof multiple and diverse biological processes such as cell cyclecontrol, genomic integrity, microtubule dynamics, celldifferentiation, metabolic networks, and autophagy Plays a majorrole in the control of cell cycle progression and genomicstability Functions in the antephase checkpoint preventingprecocious mitotic entry in response to microtubule stress agents,and hence allowing proper inheritance of chromosomes Positivelyregulates the anaphase promoting complex/cyclosome (APC/C)ubiquitin ligase complex activity by deacetylating CDC20 and FZR1,then allowing progression through mitosis Associates both withchromatin at transcriptional start sites (TSSs) and enhancers ofactive genes Plays a role in cell cycle and chromatin compactionthrough epigenetic modulation of the regulation of histone H4'Lys-20' methylation (H4K20me1) during early mitosis Specificallydeacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/Mtransition and metaphase enabling H4K20me1 deposition by KMT5Aleading to ulterior levels of H4K20me2 and H4K20me3 depositionthroughout cell cycle, and mitotic S-phase progression(PubMed:23468428) Deacetylates KMT5A modulating KMT5A chromatinlocalization during the mitotic stress response (PubMed:23468428)Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during themitotic G2/M transition Upon bacterium Listeria monocytogenesinfection, deacetylates 'Lys-18' of histone H3 in a receptortyrosine kinase MET- and PI3K/Akt-dependent manner, therebyinhibiting transcriptional activity and promoting late stages oflisteria infection (PubMed:23908241) During oocyte meiosisprogression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) andalpha-tubulin, regulating spindle assembly and chromosomealignment by influencing microtubule dynamics and kinetochorefunction Deacetylates histone H4 at 'Lys-16' (H4K16ac) at theVEGFA promoter and thereby contributes to regulate expression ofVEGFA, a key regulator of angiogenesis (PubMed:24940000)Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronalmotility, oligodendroglial cell arbor projection processes andproliferation of non-neuronal cells Phosphorylation at Ser-368 bya G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediatedalpha-tubulin deacetylation, negatively regulating cell adhesion,cell migration and neurite outgrowth during neuronaldifferentiation Deacetylates PARD3 and participates in theregulation of Schwann cell peripheral myelination formation duringearly postnatal development and during postinjury remyelinationInvolved in several cellular metabolic pathways Plays a role inthe regulation of blood glucose homeostasis by deacetylating andstabilizing phosphoenolpyruvate carboxykinase PCK1 activity inresponse to low nutrient availability Acts as a key regulator inthe pentose phosphate pathway (PPP) by deacetylating andactivating the glucose-6-phosphate G6PD enzyme, and therefore,stimulates the production of cytosolic NADPH to counteractoxidative damage Maintains energy homeostasis in response tonutrient deprivation as well as energy expenditure by inhibitingadipogenesis and promoting lipolysis Attenuates adipocytedifferentiation by deacetylating and promoting FOXO1 interactionto PPARG and subsequent repression of PPARG-dependenttranscriptional activity Plays a role in the regulation oflysosome-mediated degradation of protein aggregates by autophagyin neuronal cells Deacetylates FOXO1 in response to oxidativestress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:20543840) Deacetylates a broad rangeof transcription factors and co-regulators regulating target geneexpression Deacetylates transcriptional factor FOXO3 stimulatingthe ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination anddegradation (By similarity) Deacetylates HIF1A and thereforepromotes HIF1A degradation and inhibition of HIF1A transcriptionalactivity in tumor cells in response to hypoxia (PubMed:24681946)Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependenttranscription activation upon TNF-alpha stimulation Inhibitstranscriptional activation by deacetylating p53/TP53 and EP300(PubMed:18249187) Deacetylates also EIF5A (PubMed:22771473)Functions as a negative regulator on oxidative stress-tolerance inresponse to anoxia-reoxygenation conditions Plays a role as tumorsuppressor (PubMed:22014574) Isoform 1: Deacetylates EP300, alpha-tubulin and histoneH3 and H4 Isoform 2: Deacetylates EP300, alpha-tubulin and histoneH3 and H4 Isoform 5: Lacks deacetylation activity
Catalytic Activity (UniProt annotation)
NAD(+) + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein
Protein Sequence
MAEPDPSHPLETQAGKVQEAQDSDSDSEGGAAGGEADMDFLRNLFSQTLSLGSQKERLLDELTLEGVARYMQSERCRRVI CLVGAGISTSAGIPDFRSPSTGLYDNLEKYHLPYPEAIFEISYFKKHPEPFFALAKELYPGQFKPTICHYFMRLLKDKGL LLRCYTQNIDTLERIAGLEQEDLVEAHGTFYTSHCVSASCRHEYPLSWMKEKIFSEVTPKCEDCQSLVKPDIVFFGESLP ARFFSCMQSDFLKVDLLLVMGTSLQVQPFASLISKAPLSTPRLLINKEKAGQSDPFLGMIMGLGGGMDFDSKKAYRDVAW LGECDQGCLALAELLGWKKELEDLVRREHASIDAQSGAGVPNPSTSASPKKSPPPAKDEARTTEREKPQ

Motif information from Eukaryotic Linear Motif atlas (ELM)

(show / hide)

Gene Ontology (P: Process; F: Function and C: Component terms)

(show / hide)

GO:0000122	P:negative regulation of transcription by RNA polymerase II
GO:0000183	P:chromatin silencing at rDNA
GO:0000781	C:chromosome
GO:0003682	telomeric region
GO:0004407	F:chromatin binding
GO:0005634	F:histone deacetylase activity
GO:0005677	C:nucleus
GO:0005694	C:chromatin silencing complex
GO:0005720	C:chromosome
GO:0005730	C:nuclear heterochromatin
GO:0005737	C:nucleolus
GO:0005739	C:cytoplasm
GO:0005813	C:mitochondrion
GO:0005814	C:centrosome
GO:0005819	C:centriole
GO:0005829	C:spindle
GO:0005874	C:cytosol
GO:0005886	C:microtubule
GO:0006342	C:plasma membrane
GO:0006348	P:chromatin silencing
GO:0006351	P:chromatin silencing at telomere
GO:0006471	P:transcription
GO:0006476	DNA-templated
GO:0006914	P:protein ADP-ribosylation
GO:0007096	P:protein deacetylation
GO:0008134	P:autophagy
GO:0008270	P:regulation of exit from mitosis
GO:0008285	F:transcription factor binding
GO:0010507	F:zinc ion binding
GO:0010801	P:negative regulation of cell proliferation
GO:0014065	P:negative regulation of autophagy
GO:0016458	P:negative regulation of peptidyl-threonine phosphorylation
GO:0016575	P:phosphatidylinositol 3-kinase signaling
GO:0017136	P:gene silencing
GO:0021762	P:histone deacetylation
GO:0022011	F:NAD-dependent histone deacetylase activity
GO:0030426	P:substantia nigra development
GO:0030496	P:myelination in peripheral nervous system
GO:0031641	C:growth cone
GO:0032436	C:midbody
GO:0033010	P:regulation of myelination
GO:0033270	P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0033558	C:paranodal junction
GO:0034599	C:paranode region of axon
GO:0034979	F:protein deacetylase activity
GO:0034983	P:cellular response to oxidative stress
GO:0035035	F:NAD-dependent protein deacetylase activity
GO:0035729	P:peptidyl-lysine deacetylation
GO:0042177	F:histone acetyltransferase binding
GO:0042325	P:cellular response to hepatocyte growth factor stimulus
GO:0042826	P:negative regulation of protein catabolic process
GO:0042903	P:regulation of phosphorylation
GO:0043130	F:histone deacetylase binding
GO:0043161	F:tubulin deacetylase activity
GO:0043204	F:ubiquitin binding
GO:0043209	P:proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043219	C:perikaryon
GO:0043220	C:myelin sheath
GO:0043388	C:lateral loop
GO:0043491	C:Schmidt-Lanterman incisure
GO:0044224	P:positive regulation of DNA binding
GO:0044242	P:protein kinase B signaling
GO:0045087	C:juxtaparanode region of axon
GO:0045599	P:cellular lipid catabolic process
GO:0045836	P:innate immune response
GO:0045843	P:negative regulation of fat cell differentiation
GO:0045892	P:positive regulation of meiotic nuclear division
GO:0045944	P:negative regulation of striated muscle tissue development
GO:0046970	P:negative regulation of transcription
GO:0048012	DNA-templated
GO:0048471	P:positive regulation of transcription by RNA polymerase II
GO:0051301	F:NAD-dependent histone deacetylase activity (H4-K16 specific)
GO:0051321	P:hepatocyte growth factor receptor signaling pathway
GO:0051726	C:perinuclear region of cytoplasm
GO:0051775	P:cell division
GO:0051781	P:meiotic cell cycle
GO:0051987	P:regulation of cell cycle
GO:0061428	P:response to redox state
GO:0061433	P:positive regulation of cell division
GO:0070403	P:positive regulation of attachment of spindle microtubules to kinetochore
GO:0070446	P:negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070932	P:cellular response to caloric restriction
GO:0070933	F:NAD+ binding
GO:0071219	P:negative regulation of oligodendrocyte progenitor proliferation
GO:0071456	P:histone H3 deacetylation
GO:0071872	P:histone H4 deacetylation
GO:0072686	P:cellular response to molecule of bacterial origin
GO:0072687	P:cellular response to hypoxia
GO:0090042	P:cellular response to epinephrine stimulus
GO:0097386	C:mitotic spindle
GO:1900119	C:meiotic spindle
GO:1900195	P:tubulin deacetylation
GO:1900226	C:glial cell projection
GO:1900425	P:positive regulation of execution phase of apoptosis
GO:2000378	P:positive regulation of oocyte maturation
GO:2000777	P:negative regulation of NLRP3 inflammasome complex assembly

KEGG Pathway
Reactome Pathway

Top

SIRT2