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:
- Protein Serine/Threonine Kinase Activity
- Nf-Kappab-Inducing Kinase Activity
- Atp Binding
- Protein Homodimerization Activity
- Protein Heterodimerization Activity
Biological Processes:
- Activation Of Mapk Activity
- Regulation Of Cytokine-Mediated Signaling Pathway
- Toll-Like Receptor Signaling Pathway
- Myd88-Dependent Toll-Like Receptor Signaling Pathway
- Protein Phosphorylation
- Signal Transduction
- Transmembrane Receptor Protein Serine/Threonine Kinase Signaling Pathway
- Activation Of Nf-Kappab-Inducing Kinase Activity
- Jnk Cascade
- Aging
- Lipopolysaccharide-Mediated Signaling Pathway
- Negative Regulation Of Nf-Kappab Transcription Factor Activity
- Positive Regulation Of Type I Interferon Production
- Response To Lipopolysaccharide
- Toll-Like Receptor 2 Signaling Pathway
- Toll-Like Receptor 4 Signaling Pathway
- Toll-Like Receptor 9 Signaling Pathway
- Cellular Response To Heat
- Negative Regulation Of Apoptotic Process
- Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Positive Regulation Of Map Kinase Activity
- Innate Immune Response
- Positive Regulation Of Transcription, Dna-Templated
- Protein Autophosphorylation
- Positive Regulation Of Smooth Muscle Cell Proliferation
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Protein Oligomerization
- Nucleotide-Binding Oligomerization Domain Containing Signaling Pathway
- Interleukin-1-Mediated Signaling Pathway
- Response To Interleukin-1
- Cellular Response To Hypoxia