A0A1Y7VM56 · A0A1Y7VM56_MOUSE
- ProteinNAD-dependent protein deacylase sirtuin-5, mitochondrial
- GeneSirt5
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids350 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as Uox.
Catalytic activity
- H2O + N6-glutaryl-L-lysyl-[protein] + NAD+ = 2''-O-glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
- H2O + N6-malonyl-L-lysyl-[protein] + NAD+ = 2''-O-malonyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
- H2O + N6-succinyl-L-lysyl-[protein] + NAD+ = 2''-O-succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 58-77 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: GAGVSAESGVPTFRGAGGYW | ||||||
Binding site | 102 | substrate | ||||
Sequence: Y | ||||||
Binding site | 105 | substrate | ||||
Sequence: R | ||||||
Binding site | 140-143 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: QNID | ||||||
Active site | 158 | Proton acceptor | ||||
Sequence: H | ||||||
Binding site | 166 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 169 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 207 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 212 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 249-251 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: GTS | ||||||
Binding site | 275-277 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: NME | ||||||
Binding site | 296 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: G |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrial intermembrane space | |
Cellular Component | mitochondrial matrix | |
Cellular Component | nucleus | |
Molecular Function | NAD+ binding | |
Molecular Function | NAD-dependent protein lysine deacetylase activity | |
Molecular Function | protein-glutaryllysine deglutarylase activity | |
Molecular Function | protein-malonyllysine demalonylase activity | |
Molecular Function | protein-succinyllysine desuccinylase activity | |
Molecular Function | transferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | negative regulation of reactive oxygen species metabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNAD-dependent protein deacylase sirtuin-5, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionA0A1Y7VM56
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.
Keywords
- Cellular component
PTM/Processing
Proteomic databases
Expression
Gene expression databases
Interaction
Subunit
Monomer. Homodimer. Interacts with CPS1.
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 33-313 | Deacetylase sirtuin-type | ||||
Sequence: MARPSSNMADFRKCFANAKHIAIISGAGVSAESGVPTFRGAGGYWRKWQAQDLATPQAFARNPSQVWEFYHYRREVMRSKEPNPGHLAIAQCEARLRDQGRRVVVITQNIDELHRKAGTKNLLEIHGTLFKTRCTSCGTVAENYRSPICPALAGKGAPEPETQDARIPVDKLPRCEEAGCGGLLRPHVVWFGENLDPAILEEVDRELALCDLCLVVGTSSVVYPAAMFAPQVASRGVPVAEFNMETTPATDRFRVSLCSPGCPGTHFVDQAGLELRNLPAS |
Domain
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity.
Sequence similarities
Belongs to the sirtuin family. Class III subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length350
- Mass (Da)38,230
- Last updated2017-08-30 v1
- ChecksumB2048CF9D70044F4
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q8K2C6 | SIR5_MOUSE | Sirt5 | 310 | ||
A0A1Y7VNW0 | A0A1Y7VNW0_MOUSE | Sirt5 | 95 | ||
A0A1Y7VMJ7 | A0A1Y7VMJ7_MOUSE | Sirt5 | 79 | ||
A0A1Y7VK33 | A0A1Y7VK33_MOUSE | Sirt5 | 135 | ||
A0A1Y7VJY8 | A0A1Y7VJY8_MOUSE | Sirt5 | 289 |
Keywords
- Technical term