Summary

Name SIRT2
Full Name NAD-dependent protein deacetylase sirtuin-2
Synonyms Regulatory protein SIR2 homolog 2, SIR2-like protein 2 | SIR2L, SIR2L2
Primary ID Q8IXJ6
Links - -
Type protein
Relations 22
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: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 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 (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. 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. 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. 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 (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. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187). Deacetylates also EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor (PubMed:22014574).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ SIRT2up-regulates activity img/direct-activation.png deacetylation PGAM2 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Glycolysis and Gluconeogenesis
+ SIRT2up-regulates activity img/direct-activation.png deacetylation PGAM1 0.284
Publications: 1 Organism: Homo Sapiens
Pathways:Glycolysis and Gluconeogenesis
+ SIRT2up-regulates quantity by stabilization img/direct-activation.png deacetylation PCK1 0.438
Publications: 3 Organism: Homo Sapiens
Pathways:Glycolysis and Gluconeogenesis
+ CyclinE/CDK2down-regulates img/direct_inhibition.png phosphorylation SIRT2 0.404
Publications: 1 Organism: Homo Sapiens
+ CDC14A img/unknown.png dephosphorylation SIRT2 0.433
Publications: 1 Organism: Homo Sapiens
+ CDK2down-regulates img/direct_inhibition.png phosphorylation SIRT2 0.404
Publications: 1 Organism: Homo Sapiens
+ CDK1down-regulates img/direct_inhibition.png phosphorylation SIRT2 0.423
Publications: 1 Organism: Homo Sapiens
+ CDC14B img/unknown.png dephosphorylation SIRT2 0.415
Publications: 1 Organism: Homo Sapiens
+ SRCdown-regulates quantity by destabilization img/direct_inhibition.png phosphorylation SIRT2 0.296
Publications: 1 Organism: Homo Sapiens
+ SIRT2down-regulates img/direct_inhibition.png binding KAT2B 0.547
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ SIRT2up-regulates quantity by stabilization img/indirect-activation.png MYCN 0.385
Publications: 1 Organism: Homo Sapiens
+ SIRT2down-regulates img/direct_inhibition.png deacetylation MYOD1 0.385
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ ING1down-regulates activity img/direct_inhibition.png binding SIRT2 0.463
Publications: 1 Organism: Homo Sapiens
+ SIRT2down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation CDKN1A 0.315
Publications: 1 Organism: Homo Sapiens
+ MYCNup-regulates quantity by expression img/indirect-activation.png transcriptional regulation SIRT2 0.385
Publications: 1 Organism: Homo Sapiens
+ MYCup-regulates quantity by expression img/indirect-activation.png transcriptional regulation SIRT2 0.478
Publications: 1 Organism: Homo Sapiens
+ SIRT2down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation NEDD4 0.265
Publications: 1 Organism: Homo Sapiens
+ SIRT2up-regulates activity img/direct-activation.png deacetylation PGAM 0.284
Publications: 1 Organism: Homo Sapiens
Pathways:Glycolysis and Gluconeogenesis
+ SIRT2up-regulates quantity by expression img/indirect-activation.png transcriptional regulation AFP 0.26
Publications: 1 Organism: Homo Sapiens
+ SIRT2up-regulates quantity by stabilization img/indirect-activation.png MYC 0.478
Publications: 1 Organism: Homo Sapiens