Recombinant Human Sirtuin 2/SIRT2 Protein

Specifications

Form

Lyophilized

General info

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 : 12620231, PubMed : 16648462, PubMed : 18249187, PubMed : 18332217, PubMed : 18995842, PubMed : 20543840, PubMed : 20587414, PubMed : 21081649, PubMed : 21726808, PubMed : 21949390, PubMed : 22014574, PubMed : 22771473, PubMed : 23468428, PubMed : 23908241, PubMed : 24177535, PubMed : 24681946, PubMed : 24769394, PubMed : 24940000). 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 (PubMed : 12620231, PubMed : 16648462, PubMed : 18249187, PubMed : 18332217, PubMed : 18995842, PubMed : 20543840, PubMed : 20587414, PubMed : 21081649, PubMed : 21726808, PubMed : 21949390, PubMed : 22014574, PubMed : 22771473, PubMed : 23468428, PubMed : 23908241, PubMed : 24177535, PubMed : 24681946, PubMed : 24769394, PubMed : 24940000). Plays a major role in the control of cell cycle progression and genomic stability (PubMed : 12697818, PubMed : 16909107, PubMed : 17488717, PubMed : 17726514, PubMed : 19282667, PubMed : 23468428). Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes (PubMed : 12697818, PubMed : 16909107, PubMed : 17488717, PubMed : 17726514, PubMed : 19282667, PubMed : 23468428). Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis (PubMed : 22014574). Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes (PubMed : 23468428). 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 (PubMed : 23468428). 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 (PubMed : 23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed : 23468428). Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition (PubMed : 20587414). 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 (PubMed : 23908241). 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 (PubMed : 24940000). Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed : 24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells (PubMed : 18332217, PubMed : 18995842). 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 (PubMed : 17488717). Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination (PubMed : 21949390). Involved in several cellular metabolic pathways (PubMed : 20543840, PubMed : 21726808, PubMed : 24769394). Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability (PubMed : 21726808). 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 (PubMed : 24769394). Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis (PubMed : 20543840). Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity (PubMed : 20543840). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed : 20543840). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed : 20543840). 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 (PubMed : 24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation (PubMed : 21081649). Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed : 18249187, PubMed : 18995842). Deacetylates also EIF5A (PubMed : 22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions (PubMed : 24769394). Plays a role as tumor suppressor (PubMed : 22014574). 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 (PubMed : 25704306, PubMed : 29239724, PubMed : 32103017).. 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, at least toward known SIRT2 targets.

Sequence similarities

Belongs to the sirtuin family. Class I subfamily.

Post-translational modifications

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.. 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.. Ubiquitinated.

Subcellular localisation

Nucleus