IRAK1: a TKL kinase of the IRAK family. Involved in Toll/IL-1 signaling. One of two putative serine/threonine kinases that become associated with the interleukin-1 receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization. Extensively phosphorylated after its association with IL1-R-1. Polyubiquitinated; after cell stimulation with IL-1-beta. Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'. Partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Three isoforms of the human protein and produced by alternative splicing. Isoform 1 binds rapidly but is then degraded allowing isoform 2 to mediate a slower, more sustained response to the cytokine. Isoform 2 is inactive suggesting that the kinase activity of this enzyme is not required for IL-1 signaling. Once phosphorylated, IRAK1 recruits the adapter protein PELI1. Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.
Protein type: Kinase, protein; Protein kinase, Ser/Thr (non-receptor); EC 2.7.11.1; Protein kinase, TKL; TKL group; IRAK family
Chromosomal Location of Human Ortholog: Xq28
Cellular Component: cytoplasm; cytosol; endosome membrane; interleukin-1 receptor complex; lipid particle; nucleus; plasma membrane
Molecular Function: ATP binding; heat shock protein binding; interleukin-1 receptor binding; kinase activity; NF-kappaB-inducing kinase activity; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity; ubiquitin-protein ligase activity
Biological Process: activation of MAPK activity; activation of NF-kappaB transcription factor; activation of NF-kappaB-inducing kinase; aging; inhibition of NF-kappaB transcription factor; innate immune response; JNK cascade; lipopolysaccharide-mediated signaling pathway; MyD88-dependent toll-like receptor signaling pathway; MyD88-independent toll-like receptor signaling pathway; negative regulation of apoptosis; nerve growth factor receptor signaling pathway; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of interferon type I production; positive regulation of MAP kinase activity; positive regulation of smooth muscle cell proliferation; positive regulation of transcription, DNA-dependent; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein oligomerization; protein ubiquitination; regulation of cytokine and chemokine mediated signaling pathway; response to lipopolysaccharide; response to peptidoglycan; signal transduction; stress-activated MAPK cascade; toll-like receptor 10 signaling pathway; toll-like receptor 2 signaling pathway; toll-like receptor 3 signaling pathway; toll-like receptor 4 signaling pathway; toll-like receptor 5 signaling pathway; toll-like receptor 9 signaling pathway; toll-like receptor signaling pathway; transmembrane receptor protein serine/threonine kinase signaling pathway
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