HAMAP rule MF_03161
General rule information
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Accession | MF_03161 |
Dates | 2-APR-2012 (Created) 19-NOV-2022 (Last updated, Version 17) |
Name | Sirtuin_ClassII_euk |
Scope | Eukaryota |
Template | Q9Y6E7 (SIR4_HUMAN) |
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:Mammalia>
Protein name |
|
Gene name |
|
else
Protein name |
|
end case
Comments
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case <OC:Mammalia>
Function | Acts as NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase. Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner. Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest. In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor. Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis. Does not seem to deacetylate PC. Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1-PPARA interaction probably through the regulation of NAD(+) levels. Down-regulates insulin secretion. |
Catalytic activity | RHEA:56612: L-cysteinyl-[protein] + NAD(+) = H(+) + nicotinamide + S-(ADP-D-ribosyl)-L-cysteinyl-[protein] |
RHEA:63640: (R)-N(6)-lipoyl-L-lysyl-[protein] + H2O + NAD(+) = 2''-O-lipoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
PhysiologicalDirection=left-to-right (RHEA:63641) |
|
RHEA:70479: H2O + N(6)-biotinyl-L-lysyl-[protein] + NAD(+) = 2''-O-biotinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
PhysiologicalDirection=left-to-right (RHEA:70480) |
|
RHEA:43636: H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
EC 2.3.1.286 PhysiologicalDirection=left-to-right (RHEA:43637) |
|
Subunit | Interacts with GLUD1, IDE and SLC25A5. Interacts with DLAT and PDHX. |
Miscellaneous | According to some authors, ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant. |
else
Function | NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of acyl groups from lysine residues. |
end case
Catalytic activity | RHEA:43636: H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
EC 2.3.1.286 |
case <FTGroup:1>
Cofactor | Zn(2+) Note: Binds 1 zinc ion per subunit. |
end case
Subcellular location | Mitochondrion matrix. |
case not <OC:Mammalia> 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 II subfamily. |
Keywords
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case <OC:Mammalia>
end case
case <FTGroup:1>
end case
Gene Ontology
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GO:0005759; Cellular component: mitochondrial matrix.
GO:0034979; Molecular function: NAD-dependent protein deacetylase activity.
GO:0034979; Molecular function: NAD-dependent protein deacetylase activity.
case <OC:Mammalia>
GO:0003950; Molecular function: NAD+ ADP-ribosyltransferase activity.
end case
GO:0070403; Molecular function: NAD+ binding.
GO:0006476; Biological process: protein deacetylation.
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:Mammalia>
General | TransitM; -; 0-1; trigger=yes; |
end case
Features
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case <OC:Mammalia>
From: SIR4_HUMAN (Q9Y6E7) | ||||||||||||
Key | From | To | Description | Tag | Condition | FTGroup | ||||||
TRANSIT | Nter | 28 | Mitochondrion | |||||||||
CHAIN | 29 | Cter |
|
end case
Additional information
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Size range | 273-373 amino acids |
Related rules | None |
Fusion | None |