Aliases for IRAK1 Gene
External Ids for IRAK1 Gene
Previous GeneCards Identifiers for IRAK1 Gene
This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
GeneCards Summary for IRAK1 Gene
IRAK1 (Interleukin 1 Receptor Associated Kinase 1) is a Protein Coding gene. Diseases associated with IRAK1 include Pediatric Systemic Lupus Erythematosus and Lubs X-Linked Mental Retardation Syndrome. Among its related pathways are Activated TLR4 signalling and IL-1 Family Signaling Pathways. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is IRAK2.
UniProtKB/Swiss-Prot Summary for IRAK1 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. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. 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 the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.
The IRAKs (Interleukin-1 receptor-associated kinases) are serine-threonine kinases, EC 220.127.116.11, 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.