HAMAP rule MF_03160
General rule information
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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
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Identifier, protein and gene names
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Identifier |
|
case <OC:Vertebrata>
Protein name |
|
Gene name |
|
else
Protein name |
|
end case
Comments
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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
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case <FTGroup:1>
end case
case <OC:Vertebrata>
end case
Gene Ontology
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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.
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
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Computed features
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case not <OC:Vertebrata>
General | TransitM; -; 0-1; trigger=yes; |
end case
Features
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case <OC:Vertebrata>
From: SIR5_HUMAN (Q9NXA8) | ||||||||||||
Key | From | To | Description | Tag | Condition | FTGroup | ||||||
TRANSIT | Nter | 36 | Mitochondrion | |||||||||
CHAIN | 37 | Cter |
|
end case
Additional information
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Size range | 273-323 amino acids |
Related rules | None |
Fusion | None |