Tbio SIRT4 NAD-dependent protein lipoamidase sirtuin-4, mitochondrial

Protein Summary

Description

Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase. 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 (PubMed:25525879). 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 (PubMed:16959573, PubMed:17715127). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). 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 (By similarity). Does not seem to deacetylate PC (PubMed:23438705). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310). Down-regulates insulin secretion. This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class IV of the sirtuin family. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9Y6E7
• O43346
• Q32M33

Gene Name

• SIRT4

Ensembl ID

• ENST00000202967
• ENSP00000202967
• ENSG00000089163

Symbol

• SIR2L4
• SIR2L4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.88
biological process	0.82
kinase perturbation	0.76
protein domain	0.73
tissue sample	0.7

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Chromatin/chromatin-binding Protein / Nad-dependent Protein Lipoamidase Sirtuin-4, Mitochondrial

Protein / Hydrolase / Deacetylase / Nad-dependent Protein Lipoamidase Sirtuin-4, Mitochondrial

DTO Classes

Protein / Epigenetic Regulator / Eraser / Histone Deacetylase / Hdac Class Iii / Nad-dependent Protein Lipoamidase Sirtuin-4, Mitochondrial

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 479.88   (req: < 5)

Gene RIFs: 49   (req: <= 3)

Antibodies: 343   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 479.88   (req: >= 5)

Gene RIFs: 49   (req: > 3)

Antibodies: 343   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0