A0A7J7FBI7 · A0A7J7FBI7_DICBM
- ProteinNAD-dependent protein deacylase sirtuin-5, mitochondrial
- GeneSIRT5
- StatusUniProtKB unreviewed (TrEMBL)
- Amino acids273 (go to sequence)
- Protein existenceInferred from homology
- 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
- N6-glutaryl-L-lysyl-[protein] + NAD+ + H2O = 2''-O-glutaryl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]
- N6-malonyl-L-lysyl-[protein] + NAD+ + H2O = 2''-O-malonyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]
- N6-succinyl-L-lysyl-[protein] + NAD+ + H2O = 2''-O-succinyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 40-59 | NAD+ (UniProtKB | ChEBI) | |||
Binding site | 98 | substrate | |||
Binding site | 101 | substrate | |||
Binding site | 136-139 | NAD+ (UniProtKB | ChEBI) | |||
Active site | 154 | Proton acceptor | |||
Binding site | 162 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 165 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 177 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 190 | Zn2+ (UniProtKB | ChEBI) | |||
Binding site | 227-229 | NAD+ (UniProtKB | ChEBI) | |||
Binding site | 253-255 | NAD+ (UniProtKB | ChEBI) | |||
Binding site | 270 | NAD+ (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrion | |
Cellular Component | nucleus | |
Molecular Function | NAD+ binding | |
Molecular Function | NAD-dependent histone deacetylase activity | |
Molecular Function | protein-malonyllysine demalonylase activity | |
Molecular Function | protein-succinyllysine desuccinylase activity | |
Molecular Function | transferase activity | |
Molecular Function | zinc ion binding | |
Biological Process | protein deacetylation |
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
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Perissodactyla > Rhinocerotidae > Diceros
Accessions
- Primary accessionA0A7J7FBI7
Proteomes
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
Interaction
Subunit
Monomer. Homodimer. Interacts with CPS1.
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 15-273 | Deacetylase sirtuin-type | |||
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-98 and Arg-101) that bind to malonylated and succinylated substrates and define the specificity.
Sequence similarities
Belongs to the sirtuin family. Class III subfamily.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length273
- Mass (Da)30,146
- Last updated2021-04-07 v1
- ChecksumAD8E45E37C63BA1C
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
JACDTQ010000823 EMBL· GenBank· DDBJ | KAF5925066.1 EMBL· GenBank· DDBJ | Genomic DNA |