Sirt2
entrez
64383
canonical
uniprot
Q8VDQ8
canonical
ensembl
ENSMUSG00000015149
resolver
ensp
ENSMUSP00000072732
resolver
ensp
ENSMUSP00000132783
resolver
ensp
ENSMUSP00000147217
resolver
ensp
ENSMUSP00000232114
resolver
genesymbol
Sirt2
resolver
genesymbol_syn
Sir2l2
resolver
uniprot
E9PXF5
resolver
uniprot
Q9CXS5
resolver
uniprot
Q9EQ18
resolver
uniprot
Q9ERJ9
resolver
uniprot
U5TP50
resolver
uniprot_entry
SIR2_MOUSE
resolver
uniprot_sec
E9PXF5
resolver
uniprot_sec
Q9CXS5
resolver
uniprot_sec
Q9EQ18
resolver
uniprot_sec
Q9ERJ9
resolver
uniprot_sec
U5TP50
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation (By similarity). {ECO:0000250|UniProtKB:Q8IXJ6}.
uniprot
proteins
amino_acid_sequence
MAEPDPSDPLETQAGKVQEAQDSDSDTEGGATGGEAEMDFLRNLFTQTLGLGSQKERLLDELTLEGVTRYMQSERCRKVICLVGAGISTSAGIPDFRSPSTGLYANLEKYHLPYPEAIFEISYFKKHPEPFFALAKELYPGQFKPTICHYFIRLLKEKGLLLRCYTQNIDTLERVAGLEPQDLVEAHGTFYTSHCVNTSCRKEYTMGWMKEKIFSEATPRCEQCQSVVKPDIVFFGENLPSRFFSCMQSDFSKVDLLIIMGTSLQVQPFASLISKAPLATPRLLINKEKTGQTDPFLGMMMGLGGGMDFDSKKAYRDVAWLGDCDQGCLALADLLGWKKELEDLVRREHANIDAQSGSQAPNPSTTISPGKSPPPAKEAARTKEKEEQQ
uniprot
proteins
ec_number
2.3.1.-
uniprot
proteins
ec_number
2.3.1.286
uniprot
proteins
function
FUNCTION: NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:17521387, PubMed:17574768, PubMed:17681146, PubMed:19037106, PubMed:21791548, PubMed:21841822, PubMed:22014574, PubMed:24334550, PubMed:34059674). 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. Also deacetylates 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 (PubMed:17574768, PubMed:21791548). 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 (PubMed:17681146, PubMed:19037106). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed:17681146, PubMed:19037106). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:17681146, PubMed:19037106). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression (PubMed:34059674). Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (PubMed:17521387, PubMed:21841822). 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 stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Also deacetylates EIF5A. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of N(6)-benzoyl (benzoyl) and N(6)-methacryl (methacryl) acyl groups from lysine residues, leading to histone debenzoylation and demethacrylation, respectively (PubMed:30154464). 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). In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes (By similarity). {ECO:0000250|UniProtKB:Q8IXJ6, ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:21791548, ECO:0000269|PubMed:21841822, ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:24334550, ECO:0000269|PubMed:30154464, ECO:0000269|PubMed:34059674}.; FUNCTION: [Isoform 1]: Deacetylates alpha-tubulin. {ECO:0000269|PubMed:21791548}.; FUNCTION: [Isoform 2]: Deacetylates alpha-tubulin. {ECO:0000269|PubMed:21791548}.; FUNCTION: [Isoform 4]: Deacetylates alpha-tubulin. {ECO:0000269|PubMed:21791548}.
uniprot
proteins
mass_dalton
43256
uniprot
proteins
mutagenesis
MUTAGEN 187; /note="H->A: Abolishes deacetylation of FOXO3. Does not inhibit interaction with FOXO3."; /evidence="ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:21841822
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000250|UniProtKB:Q8IXJ6}.; PTM: 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. {ECO:0000250|UniProtKB:Q8IXJ6}.; PTM: Ubiquitinated. {ECO:0000250|UniProtKB:Q8IXJ6}.
uniprot
proteins
protein_family
Class I subfamily
uniprot
proteins
protein_family
Sirtuin family
uniprot
proteins
pubmed
11056054
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16933150
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17521387
uniprot
proteins
pubmed
17574768
uniprot
proteins
pubmed
17634366
uniprot
proteins
pubmed
17681146
uniprot
proteins
pubmed
18332217
uniprot
proteins
pubmed
19037106
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21791548
uniprot
proteins
pubmed
21841822
uniprot
proteins
pubmed
21949390
uniprot
proteins
pubmed
22014574
uniprot
proteins
pubmed
22943040
uniprot
proteins
pubmed
23468428
uniprot
proteins
pubmed
24177535
uniprot
proteins
pubmed
24334550
uniprot
proteins
pubmed
24460154
uniprot
proteins
pubmed
30154464
uniprot
proteins
pubmed
34059674
uniprot
proteins
sequence_length
389
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:24334550, ECO:0000269|PubMed:24460154}. Cytoplasm {ECO:0000269|PubMed:11056054, ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:24334550, ECO:0000269|PubMed:24460154}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:16933150}. Perikaryon {ECO:0000269|PubMed:16933150}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q8IXJ6}. Cell projection {ECO:0000269|PubMed:16933150}. Cell projection, growth cone {ECO:0000269|PubMed:18332217}. Myelin membrane {ECO:0000269|PubMed:16933150}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q8IXJ6}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:24334550}. Chromosome {ECO:0000250|UniProtKB:Q8IXJ6}. Midbody {ECO:0000269|PubMed:24334550}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000250|UniProtKB:Q8IXJ6}. Note=Localizes in the cytoplasm during most of the cell cycle except in the G2/M transition and during mitosis, where it is localized in association with chromatin and induces deacetylation of histone at 'Lys-16' (H4K16ac). Colocalizes with 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 (By similarity). Deacetylates FOXO3 in the cytoplasm (PubMed:17521387). Colocalizes with PLP1 in internodal regions of myelin sheat, at paranodal axoglial junction and Schmidt-Lanterman incisures (PubMed:16933150). Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal neurons (PubMed:16933150). Colocalizes with alpha-tubulin in neuronal growth cone (PubMed:18332217). Localizes in the cytoplasm and nucleus of germinal vesicle (GV) stage oocytes (PubMed:24334550). 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 (PubMed:24334550). {ECO:0000250|UniProtKB:Q8IXJ6, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17521387, ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:24334550}.
uniprot
proteins