Names & Taxonomy
- Uniprot ID:
- Q9NXA8
- Entry Name:
- SIR5_HUMAN
- Status:
- reviewed
- Protein Names:
- NAD-dependent protein deacylase sirtuin-5, mitochondrial (EC 3.5.1.-) (Regulatory protein SIR2 homolog 5) (SIR2-like protein 5)
- Gene Names:
- SIRT5 SIR2L5
- Gene Names Primary:
- SIRT5
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 310
- Sequence:
- MRPLQIVPSRLISQLYCGLKPPASTRNQICLKMARPSSSMADFRKFFAKAKHIVIISGAGVSAESGVPTFRGAGGYWRKWQAQDLATPLAFAHNPSRVWEFYHYRREVMGSKEPNAGHRAIAECETRLGKQGRRVVVITQNIDELHRKAGTKNLLEIHGSLFKTRCTSCGVVAENYKSPICPALSGKGAPEPGTQDASIPVEKLPRCEEAGCGGLLRPHVVWFGENLDPAILEEVDRELAHCDLCLVVGTSSVVYPAAMFAPQVAARGVPVAEFNTETTPATNRFRFHFQGPCGTTLPEALACHENETVS
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Mitochondrion matrix. Mitochondrion intermembrane space. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also present extramitochondrially: a fraction is present in the cytosol and very small amounts are also detected in the nucleus.; Isoform 1: Cytoplasm
Function
- Function:
- NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693). 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 (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). 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:
- NAD(+) + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein.
- Cofactor:
- COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide
- Enzyme Regulation:
- ENZYME REGULATION: Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity.
- Active Site:
- ACT_SITE 158 158 Proton acceptor.
- Cross Reference Drug Bank:
- DB02701 DB04786
- Gene Ontology Go:
- cytosol
mitochondrial inner membrane
mitochondrial intermembrane space
mitochondrial matrix
mitochondrion
nucleus
NAD+ ADP-ribosyltransferase activity
NAD+ binding
protein-glutaryllysine deglutarylase activity
protein-malonyllysine demalonylase activity
protein-succinyllysine desuccinylase activity
zinc ion binding
chromatin silencing
negative regulation of cardiac muscle cell apoptotic process
negative regulation of reactive oxygen species metabolic process
peptidyl-lysine deglutarylation
peptidyl-lysine demalonylation
peptidyl-lysine desuccinylation
protein ADP-ribosylation
protein deacetylation
protein deglutarylation
protein demalonylation
protein desuccinylation
regulation of ketone biosynthetic process
response to nutrient levels - Gene Ontology Biological Process:
- chromatin silencing
negative regulation of cardiac muscle cell apoptotic process
negative regulation of reactive oxygen species metabolic process
peptidyl-lysine deglutarylation
peptidyl-lysine demalonylation
peptidyl-lysine desuccinylation
protein ADP-ribosylation
protein deacetylation
protein deglutarylation
protein demalonylation
protein desuccinylation
regulation of ketone biosynthetic process
response to nutrient levels - Gene Ontology Molecular Function:
- NAD+ ADP-ribosyltransferase activity
NAD+ binding
protein-glutaryllysine deglutarylase activity
protein-malonyllysine demalonylase activity
protein-succinyllysine desuccinylase activity
zinc ion binding - Gene Ontology Cellular Component:
- cytosol
mitochondrial inner membrane
mitochondrial intermembrane space
mitochondrial matrix
mitochondrion
nucleus - Keywords:
- 3D-structure
Alternative splicing
Complete proteome
Cytoplasm
Hydrolase
Metal-binding
Mitochondrion
NAD
Nucleus
Polymorphism
Reference proteome
Transit peptide
Zinc