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IRAK1
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. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily. Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2. 4 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
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| Protein type: EC 2.7.11.1; IRAK family; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; TKL group |
| Chromosomal Location of mouse Ortholog: X A7.3|X 37.61 cM |
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Cellular Component:
cell surface; cytoplasm; cytosol; lipid droplet; membrane; nucleoplasm; nucleus; plasma membrane; protein-containing complex
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Molecular Function:
ATP binding; heat shock protein binding; identical protein binding; interleukin-1 receptor binding; kinase activity; nucleotide binding; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; protein kinase binding; protein serine/threonine kinase activity; transferase activity
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Biological Process:
activation of NF-kappaB-inducing kinase activity; cellular response to heat; cellular response to lipopolysaccharide; cytokine-mediated signaling pathway; immune system process; innate immune response; interleukin-1-mediated signaling pathway; intracellular signal transduction; JNK cascade; lipopolysaccharide-mediated signaling pathway; negative regulation of cholesterol efflux; negative regulation of DNA-templated transcription; negative regulation of NF-kappaB transcription factor activity; phosphorylation; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of JUN kinase activity; positive regulation of leukocyte adhesion to vascular endothelial cell; positive regulation of MAP kinase activity; positive regulation of NF-kappaB transcription factor activity; positive regulation of NIK/NF-kappaB signaling; positive regulation of smooth muscle cell proliferation; positive regulation of type I interferon production; protein autophosphorylation; protein phosphorylation; regulation of cytokine-mediated signaling pathway; response to interleukin-1; response to lipopolysaccharide; response to peptidoglycan; signal transduction; Toll signaling pathway; toll-like receptor 2 signaling pathway; toll-like receptor 4 signaling pathway; type I interferon-mediated signaling pathway
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Reference #:
Q62406
(UniProtKB)
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Alt. Names/Synonyms: AA408924; Il1rak; Interleukin-1 receptor-associated kinase 1; interleukin-1 receptor-associated kinase-1; interleukin-1 receptor-associated kinase-1b; IRA; IRAK; IRAK-1; Irak1; IRAK1-S; IRAK1b; mPLK; OTTMUSP00000019684; OTTMUSP00000020303; Pelle-like protein kinase; Plpk; RP23-252M19.7
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Gene Symbols: Irak1
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Molecular weight:
77,269 Da
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Basal Isoelectric point:
5.87
Predict pI for various phosphorylation states
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CST Pathways:
NF-kB Signaling
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Toll-Like Receptor Signaling
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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