IRAK4 [The Human Chemical-Genetic Interaction Map Project]

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======= IRAK4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: IRAK4
  * **<color #00a2e8>Official Name</color>**: interleukin 1 receptor associated kinase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=51135|51135]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9NWZ3|Q9NWZ3]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=IRAK4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20IRAK4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/606883|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino- mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA- IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}.

<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'>
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|interleukin-1 receptor binding|
|toll-like receptor 9 signaling pathway|
|MyD88-dependent toll-like receptor signaling pathway|
|JNK cascade|
|positive regulation of smooth muscle cell proliferation|
|neutrophil migration|
|interleukin-1-mediated signaling pathway|
|toll-like receptor signaling pathway|
|granulocyte migration|
|stress-activated MAPK cascade|
|pattern recognition receptor signaling pathway|
|myeloid leukocyte migration|
|regulation of smooth muscle cell proliferation|
|stress-activated protein kinase signaling cascade|
|cytokine production|
|positive regulation of NF-kappaB transcription factor activity|
|cellular response to interleukin-1|
|positive regulation of I-kappaB kinase/NF-kappaB signaling|
|response to interleukin-1|
|endosome membrane|
|magnesium ion binding|
|innate immune response-activating signal transduction|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|protein kinase activity|
|activation of innate immune response|
|positive regulation of DNA-binding transcription factor activity|
|positive regulation of innate immune response|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|MAPK cascade|
|leukocyte migration|
|signal transduction by protein phosphorylation|
|regulation of DNA-binding transcription factor activity|
|regulation of innate immune response|
|positive regulation of defense response|
|neutrophil mediated immunity|
|positive regulation of multi-organism process|
|myeloid leukocyte mediated immunity|
|regulation of response to biotic stimulus|
|immune response-activating signal transduction|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|activation of immune response|
|cytokine-mediated signaling pathway|
|regulation of defense response|
|innate immune response|
|leukocyte mediated immunity|
|regulation of multi-organism process|
|positive regulation of immune response|
|positive regulation of cell population proliferation|
|defense response to other organism|
|cell migration|
|protein phosphorylation|
|cellular response to cytokine stimulus|
|positive regulation of intracellular signal transduction|
|cell motility|
|localization of cell|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|regulation of immune response|
|positive regulation of immune system process|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|defense response|
|regulation of response to stress|
|ATP binding|
|movement of cell or subcellular component|
|extracellular space|
|regulation of cell population proliferation|
|regulation of immune system process|
|positive regulation of signal transduction|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of molecular function|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|immune response|
</modal>
\\

 === CRISPR Data ===
<button type='default' 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'>
No hits were found.
</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: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 17890
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.86 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='IRAK4 Expression in NALM6 Cells: 5.86'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>