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 mouse Ortholog: 15|15 E3
Cellular Component:  cytoplasm; extracellular space; nucleus; plasma membrane
Molecular Function:  ATP binding; interleukin-1 receptor binding; kinase activity; magnesium ion binding; nucleotide binding; protein binding; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process:  cytokine production; cytokine-mediated signaling pathway; immune system process; innate immune response; interleukin-1-mediated signaling pathway; intracellular signal transduction; JNK cascade; neutrophil mediated immunity; neutrophil migration; phosphorylation; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of NF-kappaB transcription factor activity; positive regulation of smooth muscle cell proliferation; protein phosphorylation; signal transduction
Reference #:  Q8R4K2 (UniProtKB)
Alt. Names/Synonyms: 8430405M07Rik; 9330209D03Rik; Interleukin-1 receptor-associated kinase 4; IRA; IRAK-4; Irak4; NY-REN; NY-REN-64; OTTMUSP00000018065
Gene Symbols: Irak4
Molecular weight: 50,872 Da
Basal Isoelectric point: 5.23  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® Total Proteins
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IRAK4

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Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene