Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 173 (16 Oct 2019)
Sequence version 2 (31 Oct 2003)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

NAD-dependent protein deacetylase sirtuin-2

Gene

Sirt2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 (PubMed:17521387, PubMed:17681146, PubMed:17574768, PubMed:19037106, PubMed:22014574, PubMed:21791548, PubMed:21841822, PubMed:24334550). 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. 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 histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. 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 (By similarity). 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 (By similarity). 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 (PubMed:22014574, PubMed:23468428).By similarity10 Publications
Isoform 1: Deacetylates alpha-tubulin.
Isoform 2: Deacetylates alpha-tubulin.
Isoform 4: Deacetylates alpha-tubulin.

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei187Proton acceptorPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi195ZincPROSITE-ProRule annotation1
Metal bindingi200ZincPROSITE-ProRule annotation1
Metal bindingi221ZincPROSITE-ProRule annotation1
Metal bindingi224ZincPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei324NAD; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi85 – 89NADBy similarity5
Nucleotide bindingi95 – 97NADBy similarity3
Nucleotide bindingi167 – 170NADBy similarity4
Nucleotide bindingi262 – 263NADBy similarity2
Nucleotide bindingi286 – 288NADBy similarity3

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransferase
Biological processAutophagy, Cell cycle, Cell division, Differentiation, Meiosis, Mitosis, Neurogenesis, Transcription, Transcription regulation
LigandMetal-binding, NAD, Zinc

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-2 (EC:2.3.1.286)
Alternative name(s):
Regulatory protein SIR2 homolog 2
SIR2-like protein 2
Short name:
mSIR2L2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Sirt2
Synonyms:Sir2l2
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 7

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:1927664 Sirt2

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

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

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi187H → A: Abolishes deacetylation of FOXO3. Does not inhibit interaction with FOXO3. 2 Publications1

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL3232691

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemovedBy similarity
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001102592 – 389NAD-dependent protein deacetylase sirtuin-2Add BLAST388

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei2N-acetylalanineBy similarity1
Modified residuei23PhosphoserineCombined sources1
Modified residuei25PhosphoserineCombined sources1
Modified residuei27PhosphothreonineCombined sources1
Modified residuei53PhosphoserineBy similarity1
Modified residuei100PhosphoserineBy similarity1
Modified residuei368PhosphoserineCombined sources1
Modified residuei372PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...
EPDi
Q8VDQ8

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
Q8VDQ8

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q8VDQ8

PeptideAtlas

More...
PeptideAtlasi
Q8VDQ8

PRoteomics IDEntifications database

More...
PRIDEi
Q8VDQ8

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q8VDQ8

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q8VDQ8

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
Q8VDQ8

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>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).

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000015149 Expressed in 292 organ(s), highest expression level in cranial nerve II

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
Q8VDQ8 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
Q8VDQ8 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with CDC20, FOXO3 and FZR1 (PubMed:17521387, PubMed:22014574). Associates with microtubule in primary cortical mature neurons (By similarity). 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 FOXO1; the interaction is disrupted upon serum-starvation or oxidative stress, leading to increased level of acetylated FOXO1 and induction of autophagy (PubMed:17681146, PubMed:19037106).

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 H2O2-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.

Interacts with the tRNA ligase SARS; recruited to the VEGFA promoter via interaction with SARS (By similarity). Isoform 2 and isoform 4 associate with microtubules in primary cortical mature neurons.

Interacts with BEX4; negatively regulates alpha-tubulin deacetylation by SIRT2 (By similarity).

By similarity5 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
211070, 24 interactors

Protein interaction database and analysis system

More...
IntActi
Q8VDQ8, 13 interactors

Molecular INTeraction database

More...
MINTi
Q8VDQ8

STRING: functional protein association networks

More...
STRINGi
10090.ENSMUSP00000072732

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
Q8VDQ8

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini65 – 340Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST276

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni116 – 120Peptide inhibitor bindingBy similarity5
Regioni232 – 301Peptide inhibitor bindingBy similarityAdd BLAST70

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi41 – 51Nuclear export signalBy similarityAdd BLAST11

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the sirtuin family. Class I subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG2682 Eukaryota
COG0846 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000157514

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000085952

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q8VDQ8

KEGG Orthology (KO)

More...
KOi
K11412

Identification of Orthologs from Complete Genome Data

More...
OMAi
FPRCDLL

Database of Orthologous Groups

More...
OrthoDBi
973532at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q8VDQ8

TreeFam database of animal gene trees

More...
TreeFami
TF106181

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.30.1600.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR029035 DHS-like_NAD/FAD-binding_dom
IPR003000 Sirtuin
IPR026591 Sirtuin_cat_small_dom_sf
IPR017328 Sirtuin_class_I
IPR026590 Ssirtuin_cat_dom

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF02146 SIR2, 1 hit

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF037938 SIR2_euk, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF52467 SSF52467, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50305 SIRTUIN, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8VDQ8-1) [UniParc]FASTAAdd to basket
Also known as: SIRT2.1

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
        10         20         30         40         50
MAEPDPSDPL ETQAGKVQEA QDSDSDTEGG ATGGEAEMDF LRNLFTQTLG
60 70 80 90 100
LGSQKERLLD ELTLEGVTRY MQSERCRKVI CLVGAGISTS AGIPDFRSPS
110 120 130 140 150
TGLYANLEKY HLPYPEAIFE ISYFKKHPEP FFALAKELYP GQFKPTICHY
160 170 180 190 200
FIRLLKEKGL LLRCYTQNID TLERVAGLEP QDLVEAHGTF YTSHCVNTSC
210 220 230 240 250
RKEYTMGWMK EKIFSEATPR CEQCQSVVKP DIVFFGENLP SRFFSCMQSD
260 270 280 290 300
FSKVDLLIIM GTSLQVQPFA SLISKAPLAT PRLLINKEKT GQTDPFLGMM
310 320 330 340 350
MGLGGGMDFD SKKAYRDVAW LGDCDQGCLA LADLLGWKKE LEDLVRREHA
360 370 380
NIDAQSGSQA PNPSTTISPG KSPPPAKEAA RTKEKEEQQ
Length:389
Mass (Da):43,256
Last modified:October 31, 2003 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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:
     1-37: Missing.

Show »
Length:352
Mass (Da):39,554
Checksum:iC67B7687704CB014
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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A140LHL5A0A140LHL5_MOUSE
NAD-dependent protein deacetylase
Sirt2
351Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti230P → L in AAG32038 (PubMed:11056054).Curated1
Sequence conflicti241S → P in AAH21439 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0087291 – 37Missing in isoform 2. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_0553296 – 76PSDPL…QSERC → R in isoform 4. CuratedAdd BLAST71
Alternative sequenceiVSP_055330236 – 389Missing in isoform 3. 1 PublicationAdd BLAST154

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
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

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS21055.1 [Q8VDQ8-1]
CCDS52165.1 [Q8VDQ8-4]
CCDS85253.1 [Q8VDQ8-2]

NCBI Reference Sequences

More...
RefSeqi
NP_001116237.1, NM_001122765.1 [Q8VDQ8-2]
NP_001116238.1, NM_001122766.1 [Q8VDQ8-4]
NP_071877.3, NM_022432.4 [Q8VDQ8-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000072965; ENSMUSP00000072732; ENSMUSG00000015149 [Q8VDQ8-1]
ENSMUST00000122915; ENSMUSP00000147217; ENSMUSG00000015149 [Q8VDQ8-2]
ENSMUST00000170068; ENSMUSP00000132783; ENSMUSG00000015149 [Q8VDQ8-4]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
64383

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:64383

UCSC genome browser

More...
UCSCi
uc009fzt.2 mouse [Q8VDQ8-1]
uc012fgx.1 mouse [Q8VDQ8-4]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF299337 mRNA Translation: AAG39256.1
AF302272
, AF302265, AF302266, AF302267, AF302268, AF302269, AF302270, AF302271 Genomic DNA Translation: AAG32038.1
AK014042 mRNA Translation: BAB29128.1
KF032392 mRNA Translation: AGZ02590.1
AC171210 Genomic DNA No translation available.
BC021439 mRNA Translation: AAH21439.1
CCDSiCCDS21055.1 [Q8VDQ8-1]
CCDS52165.1 [Q8VDQ8-4]
CCDS85253.1 [Q8VDQ8-2]
RefSeqiNP_001116237.1, NM_001122765.1 [Q8VDQ8-2]
NP_001116238.1, NM_001122766.1 [Q8VDQ8-4]
NP_071877.3, NM_022432.4 [Q8VDQ8-1]

3D structure databases

SMRiQ8VDQ8
ModBaseiSearch...

Protein-protein interaction databases

BioGridi211070, 24 interactors
IntActiQ8VDQ8, 13 interactors
MINTiQ8VDQ8
STRINGi10090.ENSMUSP00000072732

Chemistry databases

ChEMBLiCHEMBL3232691

PTM databases

iPTMnetiQ8VDQ8
PhosphoSitePlusiQ8VDQ8
SwissPalmiQ8VDQ8

Proteomic databases

EPDiQ8VDQ8
jPOSTiQ8VDQ8
PaxDbiQ8VDQ8
PeptideAtlasiQ8VDQ8
PRIDEiQ8VDQ8

Genome annotation databases

EnsembliENSMUST00000072965; ENSMUSP00000072732; ENSMUSG00000015149 [Q8VDQ8-1]
ENSMUST00000122915; ENSMUSP00000147217; ENSMUSG00000015149 [Q8VDQ8-2]
ENSMUST00000170068; ENSMUSP00000132783; ENSMUSG00000015149 [Q8VDQ8-4]
GeneIDi64383
KEGGimmu:64383
UCSCiuc009fzt.2 mouse [Q8VDQ8-1]
uc012fgx.1 mouse [Q8VDQ8-4]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
22933
MGIiMGI:1927664 Sirt2

Phylogenomic databases

eggNOGiKOG2682 Eukaryota
COG0846 LUCA
GeneTreeiENSGT00940000157514
HOGENOMiHOG000085952
InParanoidiQ8VDQ8
KOiK11412
OMAiFPRCDLL
OrthoDBi973532at2759
PhylomeDBiQ8VDQ8
TreeFamiTF106181

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
Sirt2 mouse

Protein Ontology

More...
PROi
PR:Q8VDQ8

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000015149 Expressed in 292 organ(s), highest expression level in cranial nerve II
ExpressionAtlasiQ8VDQ8 baseline and differential
GenevisibleiQ8VDQ8 MM

Family and domain databases

Gene3Di3.30.1600.10, 1 hit
InterProiView protein in InterPro
IPR029035 DHS-like_NAD/FAD-binding_dom
IPR003000 Sirtuin
IPR026591 Sirtuin_cat_small_dom_sf
IPR017328 Sirtuin_class_I
IPR026590 Ssirtuin_cat_dom
PfamiView protein in Pfam
PF02146 SIR2, 1 hit
PIRSFiPIRSF037938 SIR2_euk, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS50305 SIRTUIN, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSIR2_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q8VDQ8
Secondary accession number(s): E9PXF5
, Q9CXS5, Q9EQ18, Q9ERJ9, U5TP50
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: October 16, 2019
This is version 173 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again