Q8R104
SS
Gene name |
Sirt3 (Sir2l3) |
Protein name |
NAD-dependent protein deacetylase sirtuin-3 |
Names |
EC 2.3.1.286 , Regulatory protein SIR2 homolog 3 , SIR2-like protein 3 , mSIR2L3 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:64384 |
EC number |
2.3.1.286: Transferring groups other than amino-acyl groups |
Protein Class |
|
Descriptions
Sirtuin 2 (SIRT2) is a NAD+ dependent deacetylase that has been associated with neurodegeneration and cancer. The C-terminal region (CT) of SIRT2 functions as an autoinhibitory region that regulates the deacetylation activity of SIRT2. Phosphorylation at S331 of SIRT2 isoform 2 causes large conformational changes in the CT that enhance the autoinhibitory activity of the CT region. This serine residue is located within the naturally disordered C-terminal region (CT, residues 320-352 in isoform 2).
Autoinhibitory domains (AIDs)
Target domain |
25-296 (Catalytic core domain) |
Relief mechanism |
Others |
Assay |
|
Accessory elements
No accessory elements
References
- Li J et al. (2015) "Insight into the Mechanism of Intramolecular Inhibition of the Catalytic Activity of Sirtuin 2 (SIRT2)", PloS one, 10, e0139095
- Xu Y et al. (2014) "Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase", Cancer research, 74, 3630-42
- Finnin MS et al. (2001) "Structure of the histone deacetylase SIRT2", Nature structural biology, 8, 621-5
Autoinhibited structure
Activated structure
1 structures for Q8R104
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q8R104-F1 | Predicted | AlphaFoldDB |
No variants for Q8R104
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q8R104 | |||||
No associated diseases with Q8R104
Functions
| Description | ||
|---|---|---|
| EC Number | 2.3.1.286 | Transferring groups other than amino-acyl groups |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| mitochondrial inner membrane | The inner, i.e. lumen-facing, lipid bilayer of the mitochondrial envelope. It is highly folded to form cristae. |
| mitochondrial matrix | The gel-like material, with considerable fine structure, that lies in the matrix space, or lumen, of a mitochondrion. It contains the enzymes of the tricarboxylic acid cycle and, in some organisms, the enzymes concerned with fatty acid oxidation. |
| mitochondrion | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| enzyme binding | Binding to an enzyme, a protein with catalytic activity. |
| NAD+ binding | Binding to the oxidized form, NAD, of nicotinamide adenine dinucleotide, a coenzyme involved in many redox and biosynthetic reactions. |
| NAD-dependent histone deacetylase activity | Catalysis of the reaction |
| NAD-dependent protein deacetylase activity | Catalysis of the removal of one or more acetyl groups from a protein, requiring NAD. |
| protein lysine deacetylase activity | Catalysis of the reaction |
| sequence-specific DNA binding | Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding. |
| transferase activity | Catalysis of the transfer of a group, e.g. a methyl group, glycosyl group, acyl group, phosphorus-containing, or other groups, from one compound (generally regarded as the donor) to another compound (generally regarded as the acceptor). Transferase is the systematic name for any enzyme of EC class 2. |
| zinc ion binding | Binding to a zinc ion (Zn). |
9 GO annotations of biological process
| Name | Definition |
|---|---|
| aerobic respiration | The enzymatic release of energy from inorganic and organic compounds (especially carbohydrates and fats) which requires oxygen as the terminal electron acceptor. |
| negative regulation of ERK1 and ERK2 cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| negative regulation of peptidyl-lysine acetylation | Any process that stops, prevents or reduces the frequency, rate or extent of peptidyl-lysine acetylation. |
| negative regulation of reactive oxygen species metabolic process | Any process that stops, prevents or reduces the frequency, rate or extent of reactive oxygen species metabolic process. |
| peptidyl-lysine deacetylation | The removal of an acetyl group from an acetylated lysine residue in a peptide or protein. |
| positive regulation of ceramide biosynthetic process | Any process that activates or increases the frequency, rate or extent of ceramide biosynthetic process. |
| positive regulation of insulin secretion | Any process that activates or increases the frequency, rate or extent of the regulated release of insulin. |
| positive regulation of mitochondrial transcription | Any process that activates or increases the frequency, rate or extent of transcription occuring in the mitochondrion. |
| protein deacetylation | The removal of an acetyl group from a protein amino acid. An acetyl group is CH3CO-, derived from acetic acid. |
7 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q9I7I7 | Sirt2 | NAD-dependent protein deacetylase Sirt2 | Drosophila melanogaster (Fruit fly) | SS |
| Q8IXJ6 | SIRT2 | NAD-dependent protein deacetylase sirtuin-2 | Homo sapiens (Human) | EV |
| Q9NTG7 | SIRT3 | NAD-dependent protein deacetylase sirtuin-3, mitochondrial | Homo sapiens (Human) | SS |
| Q8VDQ8 | Sirt2 | NAD-dependent protein deacetylase sirtuin-2 | Mus musculus (Mouse) | SS |
| Q923E4 | Sirt1 | NAD-dependent protein deacetylase sirtuin-1 | Mus musculus (Mouse) | PR |
| Q5RJQ4 | Sirt2 | NAD-dependent protein deacetylase sirtuin-2 | Rattus norvegicus (Rat) | PR |
| Q7ZVK3 | sirt2 | NAD-dependent protein deacetylase sirtuin-2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MALDPLGAVV | LQSIMALSGR | LALAALRLWG | PGGGRRPISL | CVGASGGFGG | GGSSEKKFSL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| QDVAELLRTR | ACSRVVVMVG | AGISTPSGIP | DFRSPGSGLY | SNLQQYDIPY | PEAIFELGFF |
| 130 | 140 | 150 | 160 | 170 | 180 |
| FHNPKPFFML | AKELYPGHYR | PNVTHYFLRL | LHDKELLLRL | YTQNIDGLER | ASGIPASKLV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| EAHGTFVTAT | CTVCRRSFPG | EDIWADVMAD | RVPRCPVCTG | VVKPDIVFFG | EQLPARFLLH |
| 250 | 260 | 270 | 280 | 290 | 300 |
| MADFALADLL | LILGTSLEVE | PFASLSEAVQ | KSVPRLLINR | DLVGPFVLSP | RRKDVVQLGD |
| 310 | 320 | 330 | |||
| VVHGVERLVD | LLGWTQELLD | LMQRERGKLD | GQDR |