Summary of IRAK1
The gene codes for a protein, interleukin 1 receptor associated kinase 1. It is linked to the interleukin-1 receptor (IL1R) upon stimulation [R].
The Function of 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.
Protein names
Recommended name:
Interleukin-1 receptor-associated kinase 1Short name:
IRAK-1- RS1059702 (IRAK1) ??
- RS3027898 (IRAK1) ??
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Top Gene-Substance Interactions
IRAK1 Interacts with These Diseases
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Substances That Increase IRAK1
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Substances That Decrease IRAK1
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Advanced Summary
Covered on Genetics Home Reference: rheumatoid arthritis
From NCBI 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] From UniProt: 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 .
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:
Tissue specificity:
Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.
Gene Pathways:
Molecular Function:
- Atp Binding
- Nf-Kappab-Inducing Kinase Activity
- Protein Heterodimerization Activity
- Protein Homodimerization Activity
- Protein Serine/Threonine Kinase Activity
Biological Processes:
- Activation Of Mapk Activity
- Activation Of Nf-Kappab-Inducing Kinase Activity
- Aging
- Cellular Response To Heat
- Cellular Response To Hypoxia
- Innate Immune Response
- Interleukin-1-Mediated Signaling Pathway
- Jnk Cascade
- Lipopolysaccharide-Mediated Signaling Pathway
- Myd88-Dependent Toll-Like Receptor Signaling Pathway
- Negative Regulation Of Apoptotic Process
- Negative Regulation Of Nf-Kappab Transcription Factor Activity
- Nucleotide-Binding Oligomerization Domain Containing Signaling Pathway
- Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Positive Regulation Of Map Kinase Activity
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Positive Regulation Of Smooth Muscle Cell Proliferation
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Type I Interferon Production
- Protein Autophosphorylation
- Protein Oligomerization
- Protein Phosphorylation
- Regulation Of Cytokine-Mediated Signaling Pathway
- Response To Interleukin-1
- Response To Lipopolysaccharide
- Signal Transduction
- Toll-Like Receptor 2 Signaling Pathway
- Toll-Like Receptor 4 Signaling Pathway
- Toll-Like Receptor 9 Signaling Pathway
- Toll-Like Receptor Signaling Pathway
- Transmembrane Receptor Protein Serine/Threonine Kinase Signaling Pathway