SIRT4

Gene Information

Official Symbol: SIRT4
Official Name: sirtuin 4
Aliases and Previous Symbols: N/A
Entrez ID: 23409
UniProt: Q9Y6E7
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: 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. {ECO:0000255|HAMAP-Rule:MF_03161, ECO:0000269|PubMed:16959573, ECO:0000269|PubMed:17715127, ECO:0000269|PubMed:23438705, ECO:0000269|PubMed:23562301, ECO:0000269|PubMed:23663782, ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:25525879}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 0/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/25
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/15
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/14
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/7
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 12362
Expression level (log2 read counts): 0.34

Expression Distribution

lipoamidase activity
regulation of protein processing involved in protein targeting to mitochondrion
negative regulation of protein processing involved in protein targeting to mitochondrion
biotinidase activity
regulation of pyruvate dehydrogenase activity
NAD-dependent protein deacetylase activity
regulation of glutamine family amino acid metabolic process
negative regulation of protein targeting to mitochondrion
negative regulation of establishment of protein localization to mitochondrion
peptidyl-lysine deacetylation
negative regulation of fatty acid oxidation
tricarboxylic acid metabolic process
NAD+ binding
negative regulation of cardiac muscle cell apoptotic process
glutamine metabolic process
negative regulation of striated muscle cell apoptotic process
negative regulation of fatty acid metabolic process
NAD+ ADP-ribosyltransferase activity
protein ADP-ribosylation
regulation of fatty acid oxidation
negative regulation of protein maturation
negative regulation of protein processing
negative regulation of muscle cell apoptotic process
regulation of cardiac muscle cell apoptotic process
negative regulation of insulin secretion
regulation of striated muscle cell apoptotic process
negative regulation of intracellular protein transport
regulation of protein targeting to mitochondrion
negative regulation of peptide hormone secretion
protein deacetylation
negative regulation of mitochondrion organization
chromatin organization involved in negative regulation of transcription
chromatin silencing
negative regulation of intracellular transport
regulation of cellular amino acid metabolic process
protein deacylation
macromolecule deacylation
negative regulation of hormone secretion
regulation of protein processing
regulation of muscle cell apoptotic process