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: EC 2.7.11.1; IRAK family; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; TKL group
Chromosomal Location of Human Ortholog: Xq28
Cellular Component: cytoplasm; cytosol; endosome membrane; interleukin-1 receptor complex; lipid droplet; nucleus; plasma membrane
Molecular Function: ATP binding; heat shock protein binding; kinase activity; NF-kappaB-inducing kinase activity; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein serine/threonine kinase activity
Biological Process: activation of MAPK activity; activation of NF-kappaB-inducing kinase; aging; cellular response to heat; cellular response to hypoxia; JNK cascade; lipopolysaccharide-mediated signaling pathway; MyD88-dependent toll-like receptor signaling pathway; negative regulation of apoptosis; 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 interferon type I production; positive regulation of MAP kinase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of smooth muscle cell proliferation; positive regulation of transcription, DNA-templated; protein amino acid phosphorylation; protein autophosphorylation; protein oligomerization; regulation of cytokine-mediated signaling pathway; response to lipopolysaccharide; signal transduction; toll-like receptor 2 signaling pathway; toll-like receptor 4 signaling pathway; toll-like receptor 9 signaling pathway; toll-like receptor signaling pathway; transmembrane receptor protein serine/threonine kinase signaling pathway
Show more