IRAK1
Entrez ID: 3654
Full name: interleukin 1 receptor associated kinase 1
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: TKL: IRAK
Chromosomal location: Xq28
Substructure location: Gatekeeper: 288 A-loop: [N/A] G-loop: [N/A] αC-helix: [N/A]
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IRAK1
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 le...
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.
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GO - Biological processes (BP):
activation of MAPK activity, activation of NF-kappaB-inducing kinase activity, aging, cellular response to heat, cellular response to hypoxia, cellular response to lipopolysaccharide, cytokine-mediated signaling pathway, innate immune response, interleukin-1-mediated signaling pathway, intracellular...
activation of MAPK activity, activation of NF-kappaB-inducing kinase activity, aging, cellular response to heat, cellular response to hypoxia, cellular response to lipopolysaccharide, cytokine-mediated signaling pathway, innate immune response, interleukin-1-mediated signaling pathway, intracellular signal transduction, JNK cascade, lipopolysaccharide-mediated signaling pathway, MyD88-dependent toll-like receptor signaling pathway, negative regulation of apoptotic process, negative regulation of NF-kappaB transcription factor activity, nucleotide-binding oligomerization domain containing signaling pathway, positive regulation of I-kappaB kinase/NF-kappaB signaling, positive regulation of leukocyte adhesion to vascular endothelial cell, positive regulation of MAP kinase activity, positive regulation of NF-kappaB transcription factor activity, positive regulation of NIK/NF-kappaB signaling, positive regulation of smooth muscle cell proliferation, positive regulation of type I interferon production, protein autophosphorylation, protein phosphorylation, regulation of cytokine-mediated signaling pathway, response to interleukin-1, response to lipopolysaccharide, toll-like receptor 2 signaling pathway, toll-like receptor 4 signaling pathway, toll-like receptor 9 signaling pathway, toll-like receptor signaling pathway, type I interferon signaling pathway, viral process
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GO - Molecular function (MF):
ATP binding, heat shock protein binding, identical protein binding, kinase activity, NF-kappaB-inducing kinase activity, protein heterodimerization activity, protein homodimerization activity, protein kinase activity, protein serine/threonine kinase activity...
ATP binding, heat shock protein binding, identical protein binding, kinase activity, NF-kappaB-inducing kinase activity, protein heterodimerization activity, protein homodimerization activity, protein kinase activity, protein serine/threonine kinase activity
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GO - Cellular component (CC):
cytosol, endosome membrane, nucleoplasm, nucleus, interleukin-1 receptor complex, plasma membrane, cytoplasm, lipid droplet...
cytosol, endosome membrane, nucleoplasm, nucleus, interleukin-1 receptor complex, plasma membrane, cytoplasm, lipid droplet
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interleukin 1 receptor associated kinase 1
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A-loop
G-loop
αC-helix
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Kaplan plot for IRAK1 in
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*NOTE: the Kaplan plots were collected from OncoLnc