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- Table of Contents
Facts about NAD-dependent protein deacetylase sirtuin-2.
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 anxiety agents, and hence allowing appropriate inheritance of chromosomes.
Human | |
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Gene Name: | SIRT2 |
Uniprot: | Q8IXJ6 |
Entrez: | 22933 |
Belongs to: |
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sirtuin family |
EC 3.5.1; EC 3.5.1.-; FLJ35621; FLJ37491; S.cerevisiae, homolog) 2; sirtuin 2; sirtuin type 2
Mass (kDA):
43.182 kDA
Human | |
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Location: | 19q13.2 |
Sequence: | 19; NC_000019.10 (38878555..38899862, complement) |
Isoform 1 is expressed in heart, liver and skeletal muscle, weakly expressed in the cortex. Isoform 2 is strongly expressed in the cortex, weakly expressed in heart and liver. Weakly expressed in several malignancies including breast, liver, brain, kidney and prostate cancers compared to normal tissues. Weakly expressed in glioma cell lines compared to normal brain tissues (at protein level). Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Down-regulated in many gliomas suggesting that it may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network.
Nucleus. Cytoplasm, perinuclear region. Cytoplasm. Cytoplasm, cytoskeleton. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole. Cytoplasm, cytoskeleton, spindle. Midbody. Chromosome. Perikaryon. Cell projection. Cell projection, growth cone. Myelin membrane. Deacetylates FOXO3 in the cytoplasm. Colocalizes with PLP1 in internodal regions, at paranodal axoglial junction and Schmidt-Lanterman incisures of myelin sheat. Colocalizes with CDK5R1 in the perikaryon, neurites and growth cone of hippocampal n
A variety of biological tests utilize the SIRT2 marker. The antibodies can be monoclonal or polyclonal . They react to SIRT2 in various animal samples. Boster Bio uses both mouse and rabbit as models in the development of its SIRT2 antibodies. These antibodies are the most specific of all SIRT2 markers. They are also extremely specific, allowing researchers to identify and quantify levels of SIRT2 in a wide variety of biological samples.
The new lysine-defatty-acylase tests have significantly increased our understanding of SIRT2's function in the development of cardiac hypertrophy. Although the exact mechanisms that underlie this process are not known, SIRT2 is thought to play a major role in aging-related pathological cardiac hypertrophy. The presence of SIRT2 is required for the synthesis of the amino acid for the formation of new proteins.
In our previous study, SIRT2 was identified as a possible metabolic component in kidney disease caused by diabetes. The glucose levels in the kidney podocytes MPC-5 of mice were high, then normal. When cells were exposed for prolonged periods to high glucose levels, SIRT2 expression was upregulated as compared to the controls. We concluded that SIRT2 upregulation contributed to the development of diabetic nephropathy.
The present study revealed that Sirt2 plays a role in the regulation of K-Ras4a/G12V movement in a transgenic mouse. SILAC allowed us to determine the protein with a high H/L ratio. These data suggest that a genetic defect in the 3KR or SIRT2 gene may affect the ability of the protein interact with K-Ras4a.
The results of molecular tests on sirt2 proteins have shown that it inhibits AMPK and cardiomyocyte hypertrophy. In mice sirt2 gene knockouts, there was an increase in the size of the heart and decreased the cardiac ejection fraction in the study. SIRT2 overexpression prevented the aging-related hypertrophy of the heart in transgenic mice, indicating that SIRT2 plays a key role in the regulation of AMPK.
SIRT2 does not just inhibit hypertrophy, it also affects cardiac function through its ability deacetylate the cells it targets. The overexpression of SIRT2 in NRCMs significantly reduced the hypertrophic response to Ang II treatment. Additionally, the increased activity of the K-Ras4a-G12V-3KR mutation decreased the expression of Bnp, Anp and b-Mhc.
The study revealed that SIRT2 expression was differentially expressed in pluripotent as well as multipotent somatic cells. We also found that SIRT2 expression was negatively correlated with OCT4 or REX which are markers of pluripotency. SIRT2 expression was also increased in the context of spontaneous differentiation embryonic stem cell lines, but then decreased abruptly following day 9.
SIRT2 has been demonstrated to regulate inflammation and oxygenative stress. It regulates the expression of redox sensitive transcription factors such as nuclear factor kB and forkhead class O. It is involved with Akt in insulin-responsive cells, which is believed to inhibit inflammation and oxidative stress. However, further studies are needed to understand this connection. Therefore, immunocytochemistry using the SIRT2 marker is an excellent method to study the function of SIRT2 in the liver cells.
The synthetic peptide from human SIRT2 was used to detect the SIRT2 marker. This study used the immunogen p53 (379-382).
In a previous study SIRT2 was found to influence the axonal permeability and oxidative stress response of cells. We believe that SIRT2 elevated levels could function as compensatory mechanisms for neuronal oxidative stress, which could be responsible for age-related. Furthermore, these results suggest that SIRT2 could be a possible biomarker for the aging of neurodegenerative diseases, especially Alzheimer's disease.
As previously mentioned, SIRT2 is a key regulator of insulin sensitivity. The body can activate SIRT2 to treat diabetes and insulin resistance. In obese patients, SIRT2 mRNA levels were negatively correlated with waist circumference and insulin resistance indexes. Therefore, SIRT2 downregulation is linked to obesity and insulin resistance. This study suggests a new therapeutic approach for insulin-resistant patients.
The SIRT2 gene product belongs to the SIRT protein family. The size of archaebacterial and eubacterial SIRT protein is around two hundred amino acids, and both share a shared core. The SIRT protein with the highest SIRT capacity, SIRT2, is only slightly larger than the SIRT2 protein in the prokaryotic kingdom that is the smallest. Western analysis of the SIRT2 gene shows that the SIRT2 gene product isn't significantly larger than the smallest prokaryotic SIRT protein.
The SIRT gene is involved in the structure of chromatin, gene silencing, and apoptosis. In addition to its function in the progression of the cell cycle it also plays a role in the p53 pathway, a complex cell response to DNA damage. The SIRT2 marker can assist scientists to determine the presence of the gene product. To examine SIRT2 in cell culture samples, we need to perform Western Blot.
The results of this study indicate that SIRT2 protein expression is increased in the kidneys of TIF mice. We stained kidney tissue from TIF patients to determine the role of SIRT2 in tubulointerstitial Fibrosis. Western Blots were used to determine the protein expression level of SIRT2 in kidney tissues. The band densities were calculated as a proportion of UUO cells as compared to control (Sham) kidney tissues.
A comparison of FOXO1 and SIRT2 showed that both proteins interact with FOXO1 in various tissues. They play a key role in the process of gluconeogenesis as well as the response to nutrient input and environmental stress. SIRT1 as well as FOXO1 are essential in the regulation of gluconeogenesis, as well as the metabolic response, depending on the environmental and nutritional factors.
ELISA assays require the use of an antigen specific to SIRT2. Numerous biological tests can detect SIRT2 in samples using monoclonal or polyclonal antibody. Boster Bio produces antibodies that are specific to this marker by using rabbit and mouse tissues. These antibodies react with SIRT2 samples by binding to the antigen.
An ELISA kit includes the reagents needed for the test. It is a plate-based method whereby molecules are detected and quantified by enzymes that are linked to antibodies. ELISA kits come in many types. Each is based on the same principle. Boster's ELISA kit can detect native proteins. It's also tested against a range of immunogenic proteins by Boster's QC department.
Using an ELISA using the SIRT2 marker from Boster Bio, researchers have found that the enzyme is essential for the enzymatic activity of SIRT2 in human blood. The enzyme blocks SIRT1 and HMGB1 signaling in the human brains, and is a crucial player in the neuroinflammatory reaction following traumatic brain injury. Furthermore the ELISA kit has been validated for a variety of other applications.
An ELISA that employs the SIRT2 marker developed by Boster Bio uses proprietary shRNA sequences. The gene is associated with Cytin-B1 and is present in mitochondrial compartments in G2-arrested cells. Additionally it has been associated with DNA damage, which makes it crucial to check the function of this gene. In a prior study, the compound RSV (Rosvellevue) was shown to be a potent SIRT1 activator (12).
Flow Cytometry employing the SIRT2-FLAG marker could be used to determine whether cancer cells carry SIRT2. Transfected cells from HEK293T with either the SIRT2 gene in its wild-type form or a mutant version were used. The cells were washed twice using PBS Then, the cells were transfected using sirtuin-1 and FLAG. The cells were then incubated under standard cell culture conditions for 8 hours. Cells were then removed after 24 hrs and subjected to Western Blotting or SDS-PAGE analysis.
Flow Cytometry can also be used to examine the cell cycle as well as DNA content in various phases of the cell's life. This information is extremely useful in disease diagnosis and therapy prognosis in that the various stages of the cell cycle might show altered DNA content or indicate advanced cell death. The data from Flow Cytometry are stored in specific flow cytometry software and typically presented in the form of a histogram or a dot plot.
We quantified the SIRT2 expression in cells using commercially available SYBR GreenPCR kits. We used specially designed primers for SIRT2 (CCGGCCTCTATGTAACTAA-3') and b-actin (5'-CCGGCCTCTATGAAGCTCCTTC-3'). To determine the relative expression of SIRT2 We normalized its expression to b-actin levels.
Flow Cytometry with the SIRT2-marker can be a valuable tool to examine the role of SIRT2 in the metabolism of CD8+ T cells. Inhibition of GSK3b acetylation by SIRT2 enhances the differentiation of CD8+ T cells. In addition to its function in CD8+ T cell differentiation SIRT2 also regulates GSK3b Acetylation.
PMID: 10381378 by Frye R.A.; Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity.
PMID: 10393250 by Afshar G., et al. Characterization of a human gene with sequence homology to Saccharomyces cerevisiae SIR2.