IRAK4 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 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. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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: 12q12
Cellular Component:  cytosol; endosome membrane; extracellular space; plasma membrane
Molecular Function:  ATP binding; interleukin-1 receptor binding; magnesium ion binding; protein binding; protein kinase activity; protein serine/threonine kinase activity
Biological Process:  cytokine production; innate immune response; interleukin-1-mediated signaling pathway; JNK cascade; MyD88-dependent toll-like receptor signaling pathway; neutrophil mediated immunity; neutrophil migration; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of smooth muscle cell proliferation; toll-like receptor 9 signaling pathway; toll-like receptor signaling pathway
Disease: Invasive Pneumococcal Disease, Recurrent Isolated, 1; Irak4 Deficiency
Reference #:  Q9NWZ3 (UniProtKB)
Alt. Names/Synonyms: Interleukin-1 receptor-associated kinase 4; IPD1; IRAK-4; IRAK4; NY-REN-64; Q8TDF7; REN64; Renal carcinoma antigen NY-REN-64
Gene Symbols: IRAK4
Molecular weight: 51,530 Da
Basal Isoelectric point: 5.24  Predict pI for various phosphorylation states
CST Pathways:  NF-kB Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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IRAK4

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