IRAK4

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. [supplied by RefSeq]

interleukin-1 receptor-associated kinase 4

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.

Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Innate immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Interleukin-1-mediated signaling pathwayTAS:Reactome
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
JNK cascadeIEA:Ensembl
MyD88-dependent toll-like receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Neutrophil mediated immunityManual Assertion Based On ExperimentIMP:UniProtKB
Neutrophil migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIMP:MGI
Positive regulation of smooth muscle cell proliferationIEA:Ensembl
Toll-like receptor 9 signaling pathwayTAS:Reactome
Toll-like receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB

Cytoplasm

Immunodeficiency 67 (IMD67):
An autosomal recessive primary immunodeficiency characterized by recurrent, life-threatening systemic and invasive bacterial infections beginning in infancy or early childhood.

Phosphorylated.