Summary

Name IRAK4
Full Name Interleukin-1 receptor-associated kinase 4
Synonyms IRAK-4, Renal carcinoma antigen NY-REN-64
Primary ID Q9NWZ3
Links - -
Type protein
Relations 17
Pathways IL1 Signaling
Function 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 (PubMed:17878374). 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.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates img/direct-activation.png phosphorylation NCF1 0.394
Publications: 5 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation IRAK4 0.2
Publications: 4 Organism: Homo Sapiens
Pathways:IL1 Signaling
+ up-regulates activity img/direct-activation.png phosphorylation IRAK1 0.667
Publications: 4 Organism: In Vitro, Mus Musculus, Homo Sapiens
Pathways:IL1 Signaling
+ up-regulates activity img/direct-activation.png binding IRAK4 0.945
Publications: 2 Organism: Homo Sapiens
Pathways:IL1 Signaling
+ down-regulates img/direct_inhibition.png binding IRAK4 0.695
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PELI2 0.618
Publications: 1 Organism: Homo Sapiens