======= IRAK1 ======= == Gene Information == * **Official Symbol**: IRAK1 * **Official Name**: interleukin 1 receptor associated kinase 1 * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3654|3654]] * **UniProt**: [[https://www.uniprot.org/uniprot/P51617|P51617]] * **Interactions**: [[https://thebiogrid.org/search.php?search=IRAK1&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20IRAK1|Open PubMed]] * **OMIM**: [[https://omim.org/entry/300283|Open OMIM]] == Function Summary == * **Entrez Summary**: This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]. * **UniProt Summary**: 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. Is rapidly recruited by MYD88 to the receptor- signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. 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 the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}. |Pkinase Tyr| |Death| |Pkinase| |interleukin-1 receptor complex| |NF-kappaB-inducing kinase activity| |toll-like receptor 2 signaling pathway| |positive regulation of leukocyte adhesion to vascular endothelial cell| |toll-like receptor 9 signaling pathway| |activation of NF-kappaB-inducing kinase activity| |regulation of leukocyte adhesion to vascular endothelial cell| |toll-like receptor 4 signaling pathway| |nucleotide-binding oligomerization domain containing signaling pathway| |nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway| |MyD88-dependent toll-like receptor signaling pathway| |lipopolysaccharide-mediated signaling pathway| |cytoplasmic pattern recognition receptor signaling pathway| |heat shock protein binding| |cellular response to type I interferon| |type I interferon signaling pathway| |cellular response to heat| |response to type I interferon| |positive regulation of NIK/NF-kappaB signaling| |positive regulation of type I interferon production| |kinase activity| |NIK/NF-kappaB signaling| |JNK cascade| |lipid droplet| |negative regulation of NF-kappaB transcription factor activity| |positive regulation of smooth muscle cell proliferation| |interleukin-1-mediated signaling pathway| |toll-like receptor signaling pathway| |stress-activated MAPK cascade| |regulation of NIK/NF-kappaB signaling| |response to heat| |regulation of type I interferon production| |pattern recognition receptor signaling pathway| |regulation of smooth muscle cell proliferation| |stress-activated protein kinase signaling cascade| |positive regulation of NF-kappaB transcription factor activity| |activation of MAPK activity| |negative regulation of DNA-binding transcription factor activity| |regulation of cytokine-mediated signaling pathway| |intracellular receptor signaling pathway| |cellular response to interleukin-1| |regulation of response to cytokine stimulus| |response to temperature stimulus| |cellular response to lipopolysaccharide| |positive regulation of I-kappaB kinase/NF-kappaB signaling| |cellular response to hypoxia| |cellular response to molecule of bacterial origin| |protein autophosphorylation| |cellular response to decreased oxygen levels| |transmembrane receptor protein serine/threonine kinase signaling pathway| |response to interleukin-1| |endosome membrane| |cellular response to biotic stimulus| |cellular response to oxygen levels| |positive regulation of leukocyte cell-cell adhesion| |innate immune response-activating signal transduction| |regulation of I-kappaB kinase/NF-kappaB signaling| |protein kinase activity| |positive regulation of cell-cell adhesion| |activation of innate immune response| |positive regulation of MAP kinase activity| |positive regulation of DNA-binding transcription factor activity| |aging| |regulation of leukocyte cell-cell adhesion| |response to lipopolysaccharide| |response to molecule of bacterial origin| |activation of protein kinase activity| |positive regulation of protein serine/threonine kinase activity| |positive regulation of innate immune response| |regulation of MAP kinase activity| |response to hypoxia| |response to decreased oxygen levels| |positive regulation of response to biotic stimulus| |protein serine/threonine kinase activity| |MAPK cascade| |response to oxygen levels| |signal transduction by protein phosphorylation| |regulation of cell-cell adhesion| |positive regulation of cell adhesion| |regulation of DNA-binding transcription factor activity| |positive regulation of cytokine production| |regulation of innate immune response| |positive regulation of defense response| |protein heterodimerization activity| |positive regulation of multi-organism process| |regulation of protein serine/threonine kinase activity| |protein complex oligomerization| |cellular response to lipid| |regulation of response to biotic stimulus| |positive regulation of protein kinase activity| |positive regulation of MAPK cascade| |immune response-activating signal transduction| |positive regulation of kinase activity| |immune response-regulating signaling pathway| |positive regulation of response to external stimulus| |activation of immune response| |positive regulation of transferase activity| |cytokine-mediated signaling pathway| |regulation of cell adhesion| |response to bacterium| |regulation of cytokine production| |viral process| |enzyme linked receptor protein signaling pathway| |regulation of MAPK cascade| |regulation of defense response| |innate immune response| |regulation of multi-organism process| |symbiotic process| |regulation of protein kinase activity| |interspecies interaction between organisms| |response to lipid| |positive regulation of immune response| |regulation of kinase activity| |protein homodimerization activity| |negative regulation of apoptotic process| |negative regulation of programmed cell death| |positive regulation of cell population proliferation| |defense response to other organism| |protein phosphorylation| |regulation of transferase activity| |negative regulation of cell death| |cellular response to cytokine stimulus| |positive regulation of protein phosphorylation| |positive regulation of intracellular signal transduction| |cellular response to oxygen-containing compound| |positive regulation of phosphorylation| |regulation of response to external stimulus| |response to cytokine| |positive regulation of phosphorus metabolic process| |positive regulation of phosphate metabolic process| |negative regulation of molecular function| |positive regulation of immune system process| |regulation of immune response| |response to abiotic stimulus| |positive regulation of protein modification process| |phosphorylation| |response to other organism| |response to external biotic stimulus| |response to biotic stimulus| |defense response| |positive regulation of catalytic activity| |regulation of protein phosphorylation| |regulation of response to stress| |ATP binding| |positive regulation of transcription, DNA-templated| |regulation of apoptotic process| |response to oxygen-containing compound| |protein-containing complex assembly| |regulation of programmed cell death| |regulation of phosphorylation| |positive regulation of cellular protein metabolic process| |regulation of cell population proliferation| |positive regulation of nucleic acid-templated transcription| |positive regulation of RNA biosynthetic process| |regulation of immune system process| |positive regulation of signal transduction| |regulation of cell death| |intracellular signal transduction| |cellular response to stress| |positive regulation of protein metabolic process| |positive regulation of RNA metabolic process| |positive regulation of multicellular organismal process| |positive regulation of molecular function| |regulation of phosphate metabolic process| |regulation of phosphorus metabolic process| |positive regulation of cell communication| |positive regulation of signaling| |regulation of intracellular signal transduction| |regulation of protein modification process| |protein-containing complex subunit organization| |immune response| |positive regulation of nucleobase-containing compound metabolic process| |positive regulation of macromolecule biosynthetic process| |positive regulation of cellular biosynthetic process| |positive regulation of gene expression| |positive regulation of biosynthetic process| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp290|LLY-283 2.6μM R06 exp290]]|-1.85| |[[:results:exp390|Pifithrin-alpha 20μM R07 exp390]]|-1.78| |[[:results:exp52|Ribavirin 10μM R01 exp52]]|-1.71| |[[:results:exp84|UM0125461 0.74μM R02 exp84]]|1.92| No correlation found to any other genes in chemogenomics. Global Fraction of Cell Lines Where Essential: 0/694 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/26| |bone|0/26| |breast|0/30| |central nervous system|0/49| |cervix|0/4| |colorectal|0/17| |esophagus|0/11| |fibroblast|0/1| |gastric|0/14| |kidney|0/18| |liver|0/19| |lung|0/72| |lymphocyte|0/16| |ovary|0/25| |pancreas|0/22| |peripheral nervous system|0/15| |plasma cell|0/12| |prostate|0/1| |skin|0/20| |soft tissue|0/9| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/28| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 9303 * **Expression level (log2 read counts)**: 7.29 {{:chemogenomics:nalm6 dist.png?nolink |}}