IRAK2 Gene - Function, Mutations, and Disease Associations

IRAK2 (Interleukin-1 Receptor-Associated Kinase 2) encodes a serine/threonine kinase that plays a critical role in the signaling pathways of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). Upon receptor activation, IRAK2 is recruited to the receptor complex via MyD88 and undergoes phosphorylation, leading to the activation of NF-kappaB and MAP kinases. Unlike IRAK1 and IRAK4, IRAK2 lacks intrinsic kinase activity but acts as a scaffold to propagate downstream signals. It is essential for the production of pro-inflammatory cytokines and is implicated in immune responses, inflammatory diseases, and cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Toll-like receptor signaling pathway (KEGG: hsa04620)

• IL-1 signaling pathway (Reactome: R-HSA-446652)

• MyD88-dependent cascade (Reactome: R-HSA-166058)

• NF-kappaB signaling (Reactome: R-HSA-975871)

IRAK2 is a 590-amino acid protein containing an N-terminal death domain and a central kinase-like domain that lacks catalytic activity. It functions primarily as a scaffold in the TLR/IL-1R signaling cascade. Upon receptor activation, IRAK2 interacts with MyD88 and IRAK4, leading to the recruitment of TRAF6 and subsequent activation of TAK1, IKK, and NF-kappaB. IRAK2 is widely expressed in immune tissues and is upregulated in response to inflammatory stimuli. Its dysregulation is linked to cancer, autoimmune diseases, and infectious diseases.