Aliases for IRAK4 Gene
External Ids for IRAK4 Gene
Previous GeneCards Identifiers for IRAK4 Gene
This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
GeneCards Summary for IRAK4 Gene
IRAK4 (Interleukin 1 Receptor Associated Kinase 4) is a Protein Coding gene. Diseases associated with IRAK4 include Irak4 Deficiency and Invasive Pneumococcal Disease, Recurrent Isolated, 1. Among its related pathways are Bacterial infections in CF airways and Toll-like receptor signaling pathway. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is IRAK1.
UniProtKB/Swiss-Prot for IRAK4 Gene
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.
The IRAKs (Interleukin-1 receptor-associated kinases) are serine-threonine kinases, EC 18.104.22.168, that are essential regulators of IL-1R and TLR-mediated signaling. Four IRAK isoforms have been identified to date, IRAK1, IRAK2, IRAK3 (IRAK-M) and IRAK4.