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  3. IRAK1

IRAK1 (Interleukin 1 receptor associated kinase 1)

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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].

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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 1

Short name:

IRAK-1

IRAK1 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS1059702 (IRAK1) ??
  2. RS3027898 (IRAK1) ??

Top Gene-Substance Interactions

IRAK1 Interacts with These Diseases

Disease Score

Substances That Increase IRAK1

Substances Interaction Organism Category

Substances That Decrease IRAK1

Substances Interaction Organism Category

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

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • NF-kappaB
  • STAT3
  • NF-kappaB1
  • c-Rel
  • YY1
  • GATA-3
  • RelA

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:

  • Immune System
  • Signal Transduction
  • Measles
  • Toll-like receptor signaling pathway
  • Tuberculosis
  • Neurotrophin signaling pathway
  • Apoptosis
  • Chagas disease (American trypanosomiasis)
  • Toxoplasmosis
  • TRAF6 Mediated Induction of proinflammatory cytokines
  • Leishmaniasis

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
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| GW7_13706| I79_013952| Il1rak| interleukin-1 receptor-associated kinase 1| interleukin-1 receptor-associated kinase-1b| interleukin receptor associated kinase 1| irak| IRAK-1| IRAK1b| IRAK1-S| M91_10308| MDA_GLEAN10006512| mPLK| PAL_GLEAN10001422| pelle| Pelle homolog| pelle-like protein kinase| Plpk| RGD1563841| irak1

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