L8IVE9 · L8IVE9_9CETA

  • Protein
    NAD-dependent protein lipoamidase sirtuin-4, mitochondrial
  • Gene
    SIRT4
  • Status
    UniProtKB unreviewed (TrEMBL)
  • Amino acids
  • Protein existence
    Inferred from homology
  • Annotation score
    5/5

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

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site63-83NAD+ (UniProtKB | ChEBI)
Binding site144-147NAD+ (UniProtKB | ChEBI)
Active site162Proton acceptor
Binding site170Zn2+ (UniProtKB | ChEBI)
Binding site173Zn2+ (UniProtKB | ChEBI)
Binding site221Zn2+ (UniProtKB | ChEBI)
Binding site224Zn2+ (UniProtKB | ChEBI)
Binding site261-263NAD+ (UniProtKB | ChEBI)
Binding site287-289NAD+ (UniProtKB | ChEBI)
Binding site305NAD+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrial matrix
Cellular Componentnucleus
Molecular Functionlipoamidase activity
Molecular FunctionNAD+ binding
Molecular FunctionNAD+-protein poly-ADP-ribosyltransferase activity
Molecular FunctionNAD+-protein-cysteine ADP-ribosyltransferase activity
Molecular FunctionNAD-dependent protein biotinidase activity
Molecular FunctionNAD-dependent protein lipoamidase activity
Molecular FunctionNAD-dependent protein lysine deacetylase activity
Molecular Functionzinc ion binding
Biological ProcessDNA damage response
Biological Processglutamine metabolic process
Biological Processnegative regulation of fatty acid oxidation
Biological Processnegative regulation of insulin secretion
Biological Processpeptidyl-lysine deacetylation
Biological Processpositive regulation of lipid biosynthetic process
Biological Processregulation of glutamine family amino acid metabolic process
Biological Processregulation of pyruvate dehydrogenase activity
Biological Processtricarboxylic acid metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    NAD-dependent protein lipoamidase sirtuin-4, mitochondrial
  • EC number
  • Alternative names
    • NAD-dependent ADP-ribosyltransferase sirtuin-4
      (EC:2.4.2.-
      ) . EC:2.4.2.- (UniProtKB | ENZYME | Rhea)
    • NAD-dependent protein biotinylase sirtuin-4
      (EC:2.3.1.-
      ) . EC:2.3.1.- (UniProtKB | ENZYME | Rhea)
    • NAD-dependent protein deacetylase sirtuin-4
      (EC:2.3.1.286
      ) . EC:2.3.1.286 (UniProtKB | ENZYME | Rhea)
    • Regulatory protein SIR2 homolog 4
    • SIR2-like protein 4

Gene names

    • Name
      SIRT4
    • ORF names
      M91_08078

Organism names

  • Taxonomic identifier
  • Organism
  • Strain
    • yakQH1
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos

Accessions

  • Primary accession
    L8IVE9

Proteomes

Subcellular Location

Keywords

Interaction

Subunit

Interacts with GLUD1, IDE and SLC25A5. Interacts with DLAT and PDHX.

Protein-protein interaction databases

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain38-315Deacetylase sirtuin-type

Sequence similarities

Belongs to the sirtuin family. Class II subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    315
  • Mass (Da)
    35,569
  • Last updated
    2013-04-03 v1
  • Checksum
    3AAEDB386D1CE64A
MRMSFGLTFKRTAKVHWRANFSQQCSLRSTGLFVPPSPPLDPEKVKELQRFITLSKRLLVMTGAGISTESGIPDYRSEKVGLYARTDRRPIQHGDFVRSAPVRQRYWARNFVGWPQFSSHQPNPAHWALSNWERLGKLHWLVTQNVDALHTKAGSQRLTELHGCMHRVLCLDCGEQTPRGVLQERFQVLNPTWSAEAHGLAPDGDVFLTEEEVQSFQVPSCSRCGGPLKPDVVFFGDTVKPDKVDFVHKRVKEADSLLVVGSSLQVYSGYRFILTAREKKLPIVILNIGPTRSDDLASLKLDSRCGELLPLIDPR

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
JH880719
EMBL· GenBank· DDBJ
ELR59414.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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