A0A2K5H6V3 · A0A2K5H6V3_COLAP
- ProteinNAD-dependent protein lipoamidase sirtuin-4, mitochondrial
- GeneSIRT4
- StatusUniProtKB unreviewed (TrEMBL)
- Amino acids314 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
Function
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.
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.
Catalytic activity
- H2O + N6-[(R)-lipoyl]-L-lysyl-[protein] + NAD+ = 2''-O-lipoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
- H2O + N6-biotinyl-L-lysyl-[protein] + NAD+ = 2''-O-biotinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide
- L-cysteinyl-[protein] + NAD+ = H+ + nicotinamide + S-(ADP-D-ribosyl)-L-cysteinyl-[protein]
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 62-82 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: GAGISTESGIPDYRSEKVGLY | ||||||
Binding site | 143-146 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: QNVD | ||||||
Active site | 161 | Proton acceptor | ||||
Sequence: H | ||||||
Binding site | 169 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 172 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 220 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 223 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 260-262 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: GSS | ||||||
Binding site | 286-288 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: NIG | ||||||
Binding site | 304 | NAD+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Cellular Component | nucleus | |
Molecular Function | NAD+ ADP-ribosyltransferase activity | |
Molecular Function | NAD+ binding | |
Molecular Function | NAD+- protein-cysteine ADP-ribosyltransferase activity | |
Molecular Function | NAD-dependent protein biotinidase activity | |
Molecular Function | NAD-dependent protein lipoamidase activity | |
Molecular Function | NAD-dependent protein lysine deacetylase activity | |
Molecular Function | zinc ion binding |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNAD-dependent protein lipoamidase sirtuin-4, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Colobinae > Colobus
Accessions
- Primary accessionA0A2K5H6V3
Proteomes
Subcellular Location
Interaction
Subunit
Interacts with GLUD1, IDE and SLC25A5. Interacts with DLAT and PDHX.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 37-314 | Deacetylase sirtuin-type | ||||
Sequence: PPLDPEKVKELQRFITLSKRLLVMTGAGISTESGIPDYRSEKVGLYARTDRRPIQHGDFVRSAPIRQRYWARNFVGWPQFSSHQPNPAHWALSTWEKLGKLYWLVTQNVDALHTKAGSQRLTELHGCMHRVLCLDCGEQTPRGVLQERFQVLNPTWSAEAYGLAPDGDVFLSEEQVRSFQVPSCIQCGGHLKPDVVFFGDTVNPDKVDFVHKRVKEADSLLVVGSSLQVYSSYRFILTAREKKLPIAILNIGPTRSDDLACLKLNSRCGELLPLIDPR |
Sequence similarities
Belongs to the sirtuin family. Class II subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length314
- Mass (Da)35,336
- Last updated2018-03-28 v1
- ChecksumF9220A82A87145A3
Keywords
- Technical term