SIRT4 [The Human Chemical-Genetic Interaction Map Project]

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======= SIRT4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SIRT4
  * **<color #00a2e8>Official Name</color>**: sirtuin 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=23409|23409]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9Y6E7|Q9Y6E7]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SIRT4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SIRT4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604482|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|SIR2|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|regulation of protein maturation|
|chromatin organization involved in regulation of transcription|
|glutamine family amino acid metabolic process|
|regulation of establishment of protein localization to mitochondrion|
|positive regulation of lipid biosynthetic process|
|regulation of cellular amine metabolic process|
|negative regulation of gene expression, epigenetic|
|regulation of protein targeting|
|negative regulation of lipid metabolic process|
|regulation of fatty acid metabolic process|
|negative regulation of small molecule metabolic process|
|regulation of oxidoreductase activity|
|negative regulation of cellular protein localization|
|negative regulation of protein secretion|
|negative regulation of peptide secretion|
|positive regulation of lipid metabolic process|
|gene silencing|
|regulation of cellular ketone metabolic process|
|regulation of insulin secretion|
|regulation of mitochondrion organization|
|negative regulation of protein transport|
|negative regulation of establishment of protein localization|
|regulation of lipid biosynthetic process|
|cellular response to hypoxia|
|cellular response to decreased oxygen levels|
|negative regulation of secretion by cell|
|alpha-amino acid metabolic process|
|regulation of peptide hormone secretion|
|cellular response to oxygen levels|
|regulation of intracellular protein transport|
|negative regulation of secretion|
|regulation of gene expression, epigenetic|
|regulation of hormone secretion|
|cellular amino acid metabolic process|
|peptidyl-lysine modification|
|response to hypoxia|
|regulation of intracellular transport|
|negative regulation of proteolysis|
|response to decreased oxygen levels|
|mitochondrial matrix|
|negative regulation of organelle organization|
|response to oxygen levels|
|regulation of lipid metabolic process|
|mitochondrial inner membrane|
|regulation of small molecule metabolic process|
|mitochondrion organization|
|regulation of protein secretion|
|negative regulation of transport|
|regulation of peptide secretion|
|regulation of hormone levels|
|regulation of cellular protein localization|
|chromatin organization|
|negative regulation of cellular component organization|
|regulation of protein transport|
|regulation of proteolysis|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|cellular response to DNA damage stimulus|
|regulation of secretion|
|zinc ion binding|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|carboxylic acid metabolic process|
|regulation of cellular localization|
|negative regulation of cell death|
|oxoacid metabolic process|
|organic acid metabolic process|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|chromosome organization|
|negative regulation of protein metabolic process|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|mitochondrion|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|regulation of cell death|
|cellular response to stress|
|negative regulation of gene expression|
|small molecule metabolic process|
|regulation of transport|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|1.72|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12362
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 0.34 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SIRT4 Expression in NALM6 Cells: 0.34'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>