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

Publication

PubMed ID:
10381378 14702039 17974005 14574404 15489334 16079181 18680753 21269460 21143562 21908771 23028781 24140062 23806337 24703693 24275569 17355872 22076378 22767592 22849721 23185430