A0A2K5H6V3 · A0A2K5H6V3_COLAP

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.

TypeIDPosition(s)Description
Binding site62-82NAD+ (UniProtKB | ChEBI)
Binding site143-146NAD+ (UniProtKB | ChEBI)
Active site161Proton acceptor
Binding site169Zn2+ (UniProtKB | ChEBI)
Binding site172Zn2+ (UniProtKB | ChEBI)
Binding site220Zn2+ (UniProtKB | ChEBI)
Binding site223Zn2+ (UniProtKB | ChEBI)
Binding site260-262NAD+ (UniProtKB | ChEBI)
Binding site286-288NAD+ (UniProtKB | ChEBI)
Binding site304NAD+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentmitochondrial matrix
Cellular Componentnucleus
Molecular FunctionNAD+ ADP-ribosyltransferase activity
Molecular FunctionNAD+ binding
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

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

Organism names

Accessions

  • Primary accession
    A0A2K5H6V3

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
Domain37-314Deacetylase sirtuin-type

Sequence similarities

Belongs to the sirtuin family. Class II subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    314
  • Mass (Da)
    35,336
  • Last updated
    2018-03-28 v1
  • Checksum
    F9220A82A87145A3
MKMSFGLTFRSAKGRWIANPSWQCSKASIGLFVPASPPLDPEKVKELQRFITLSKRLLVMTGAGISTESGIPDYRSEKVGLYARTDRRPIQHGDFVRSAPIRQRYWARNFVGWPQFSSHQPNPAHWALSTWEKLGKLYWLVTQNVDALHTKAGSQRLTELHGCMHRVLCLDCGEQTPRGVLQERFQVLNPTWSAEAYGLAPDGDVFLSEEQVRSFQVPSCIQCGGHLKPDVVFFGDTVNPDKVDFVHKRVKEADSLLVVGSSLQVYSSYRFILTAREKKLPIAILNIGPTRSDDLACLKLNSRCGELLPLIDPR

Keywords

Sequence databases

Genome annotation databases

Similar Proteins

Disclaimer

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