Summary of IRAK4
The gene codes for a protein, interleukin 1 receptor associated kinase 4. Mutations cause IRAK4 deficiency and pneumococcal disease [R].
The Function of 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 (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.
Protein names
Recommended name:
Interleukin-1 receptor-associated kinase 4Short name:
IRAK-4Alternative name(s):
Renal carcinoma antigen NY-REN-64- RS1461567 (IRAK4) ??
- RS4251424 (IRAK4) ??
- RS4251513 (IRAK4) ??
- RS4251545 (IRAK4) ??
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Top Gene-Substance Interactions
IRAK4 Interacts with These Diseases
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Substances That Increase IRAK4
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Substances That Decrease IRAK4
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Advanced Summary
IRAK-4 deficiency At least 20 mutations in the IRAK4 gene have been identified in people with IRAK-4 deficiency, an immune system disorder that leads to recurrent invasive bacterial infections. These gene mutations lead to an abnormally short, nonfunctional IRAK-4 protein or no protein at all. The loss of functional IRAK-4 protein blocks the initiation of inflammation in response to pathogens or cytokines that would normally help fight the infections. Because the early immune response is insufficient, bacterial infections occur often and become severe and invasive.
The IRAK4 gene provides instructions for making a protein that plays an important role in innate immunity, which is the body's early, nonspecific response to foreign invaders (pathogens). The IRAK-4 protein is part of a signaling pathway that is involved in early recognition of pathogens and the initiation of inflammation to fight infection. In particular, the IRAK-4 protein relays signals from proteins called Toll-like receptors and IL-1 receptor-related proteins. As one of the first lines of defense against infection, Toll-like receptors recognize patterns that are common to many pathogens, rather than recognizing specific pathogens, and stimulate a quick immune response. The IL-1 receptor and related proteins recognize immune system proteins called cytokines that signal the need for an immune response. The resulting signaling pathway triggers inflammation, a nonspecific immune response that helps fight infection.
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
Molecular Function:
Biological Processes:
- Cytokine Production
- Toll-Like Receptor Signaling Pathway
- Neutrophil Mediated Immunity
- Myd88-Dependent Toll-Like Receptor Signaling Pathway
- Jnk Cascade
- Cytokine-Mediated Signaling Pathway
- Toll-Like Receptor 9 Signaling Pathway
- Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Innate Immune Response
- Positive Regulation Of Smooth Muscle Cell Proliferation
- Neutrophil Migration