interleukin 1 receptor associated kinase 4
Annotations refreshed 9 hours ago.
Diagnostic Grade (Green)
COVID-19 research
BIALLELIC, autosomal or pseudoautosomalPrimary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomalImmunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency
immunodeficiency 67
inborn error of immunity
autoimmune disorder of central nervous system
immunodeficiency 33
congenital dyserythropoietic anemia
pericarditis
neurodegenerative disease
hereditary disease
alcohol drinking
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
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
IRAK4 · Q9NWZ3
Mean pLDDT
83.9/ 100
Confident
460 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
