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: cell surface; cytoplasm; cytosol; endosome membrane; extracellular space; extrinsic component of plasma membrane; nucleus; plasma membrane

Molecular Function: ATP binding; interleukin-1 receptor binding; kinase activity; magnesium ion binding; protein binding; protein kinase binding; protein serine kinase activity; protein serine/threonine kinase activity

Biological Process: cellular response to lipopolysaccharide; cytokine-mediated signaling pathway; innate immune response; interleukin-1-mediated signaling pathway; intracellular signal transduction; 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; protein phosphorylation; Toll signaling pathway; toll-like receptor 4 signaling pathway; toll-like receptor 9 signaling pathway; toll-like receptor signaling pathway

Disease: Irak4 Deficiency

Reference #: Q9NWZ3 (UniProtKB)

Alt. Names/Synonyms: IMD67; interleukin 1 receptor associated kinase 4; 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, siRNAs or Recombinant Proteins from Cell Signaling Technology^®

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IRAK4

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