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HAMAP rule MF_03160

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General rule information [?]

Accession MF_03160
Dates 2-APR-2012 (Created)
19-NOV-2022 (Last updated, Version 13)
Name Sirtuin_ClassIII_euk
Scope
Eukaryota
Templates Q9NXA8 (SIR5_HUMAN); O28597 (NPD1_ARCFU); Q8IE47 (SIR2A_PLAF7); Q8K2C6 (SIR5_MOUSE): [Recover all]
case <OC:Eukaryota>
Triggered by
end case


Propagated annotation [?]


Identifier, protein and gene names [?]

Identifier
SIR5
case <OC:Vertebrata>
Protein name
RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial;
EC 2.3.1.-;
AltName: Full=Regulatory protein SIR2 homolog 5;
AltName: Full=SIR2-like protein 5;
Flags: Precursor;
Gene name
SIRT5
else
Protein name
RecName: Full=NAD-dependent protein deacylase;
EC 2.3.1.-;
AltName: Full=Regulatory protein SIR2 homolog 5;
end case

Comments [?]

case <FTGroup:3> and <OC:Mammalia>
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 (By similarity). 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.
Subunit Monomer. Homodimer. Interacts with CPS1.
else case <FTGroup:3> and not <OC:Mammalia>
Function NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
else
Function NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
end case
case <FTGroup:3>
Catalytic activity RHEA:47672: H2O + N(6)-malonyl-L-lysyl-[protein] + NAD(+) = 2''-O-malonyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
RHEA:47668: H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O-succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
RHEA:47664: H2O + N(6)-glutaryl-L-lysyl-[protein] + NAD(+) = 2''-O-glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
end case
case <FTGroup:1>
Cofactor Zn(2+)
Note: Binds 1 zinc ion per subunit.
end case
case <OC:Vertebrata>
Subcellular location Mitochondrion. Cytoplasm, cytosol. Nucleus. Note=Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.
else
Subcellular location Mitochondrion.
end case
case <FTGroup:3>
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.
end case
case not <OC:Vertebrata> and not <AnyFeature:TransitM>
Miscellaneous This protein may be expected to contain an N-terminal transit peptide but none has been predicted.
end case
Similarity Belongs to the sirtuin family. Class III subfamily.

Keywords [?]

Transferase
Mitochondrion
NAD
case <FTGroup:1>
Metal-binding
Zinc
end case
case <OC:Vertebrata>
Cytoplasm
Nucleus
Transit peptide
end case

Gene Ontology [?]

GO:0005739; Cellular component: mitochondrion.
GO:0034979; Molecular function: NAD-dependent protein deacetylase activity.
GO:0070403; Molecular function: NAD+ binding.
GO:0036054; Molecular function: protein-malonyllysine demalonylase activity.
GO:0036055; Molecular function: protein-succinyllysine desuccinylase activity.
GO:0006476; Biological process: protein deacetylation.
case <FTGroup:1>
GO:0008270; Molecular function: zinc ion binding.
end case

Cross-references [?]

PROSITE PS50305; SIRTUIN; 1; trigger=PRU00236;
Pfam PF02146; SIR2; 1;

Computed features [?]

case not <OC:Vertebrata>
General TransitM; -; 0-1; trigger=yes;
end case

Features [?]

case <OC:Vertebrata>
From: SIR5_HUMAN (Q9NXA8)
Key     From     To       Description   Tag   Condition   FTGroup
TRANSIT     Nter     36       Mitochondrion        
CHAIN     37     Cter              
end case
BINDING     58     77       /ligand="NAD(+)" /ligand_id="ChEBI:CHEBI:57540     G-A-G-x-S-[AK]-x-S-G-[ILV]-x-T-x(7,8)-W  
BINDING     140     143       /ligand="NAD(+)" /ligand_id="ChEBI:CHEBI:57540     Q-N-[IV]-[DE]  
BINDING     249     251       /ligand="NAD(+)" /ligand_id="ChEBI:CHEBI:57540     G-[TS]-S  
BINDING (Optional)     275     277       /ligand="NAD(+)" /ligand_id="ChEBI:CHEBI:57540     N-x(2)  
ACT_SITE     158     158       Proton acceptor     H  
BINDING (Optional)     166     166       /ligand="Zn(2+)" /ligand_id="ChEBI:CHEBI:29105     C   1
BINDING (Optional)     169     169       /ligand="Zn(2+)" /ligand_id="ChEBI:CHEBI:29105     C   2
BINDING (Optional)     207     207       /ligand="Zn(2+)" /ligand_id="ChEBI:CHEBI:29105     C   1
BINDING (Optional)     212     212       /ligand="Zn(2+)" /ligand_id="ChEBI:CHEBI:29105     C   2
BINDING (Optional)     102     102       /ligand="substrate     Y   3
BINDING (Optional)     105     105       /ligand="substrate     R   3
BINDING     293     293       /ligand="NAD(+)" /ligand_id="ChEBI:CHEBI:57540        

Additional information [?]

Size range 273-323 amino acids
Related rules None
Fusion None


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