Summary

Name IRAK1
Full Name Interleukin-1 receptor-associated kinase 1
Synonyms IRAK-1 | IRAK
Primary ID P51617
Links - -
Type protein
Relations 32
Pathways Innate Immune Response, IL1 Signaling , Macrophage: IL1 beta, Macrophage: Polarization and myogenesis, Satellite: IL1 , Toll like receptors
Function 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.

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Modifications Tables

Relations

Regulator Mechanism target score
+ up-regulates activity img/direct-activation.png ubiquitination IRAK1 0.911
Publications: 2 Organism: Homo Sapiens
Pathways:Innate Immune Response, IL1 Signaling , Toll like receptors
+ up-regulates activity img/direct-activation.png phosphorylation PELI1 0.755
Publications: 6 Organism: Homo Sapiens
Pathways:IL1 Signaling
+ up-regulates activity img/direct-activation.png phosphorylation IRAK1 0.2
Publications: 5 Organism: In Vitro, Homo Sapiens, Chlorocebus Aethiops
Pathways:Innate Immune Response, IL1 Signaling , Toll like receptors
+ up-regulates activity img/direct-activation.png phosphorylation IRAK1 0.667
Publications: 4 Organism: In Vitro, Mus Musculus, Homo Sapiens
Pathways:IL1 Signaling
+ up-regulates activity img/direct-activation.png phosphorylation GLIPR2 0.335
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation STAT3 0.571
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation IRAK1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation IRAK1 0.396
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding TRAF6 0.911
Publications: 2 Organism: Homo Sapiens
Pathways:Innate Immune Response, IL1 Signaling , Toll like receptors
+ down-regulates img/direct_inhibition.png binding IRAK1 0.416
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation PELI3 0.713
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png IRAK1 0.91
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling
+ up-regulates quantity by expression img/direct-activation.png ubiquitination IRAK1 0.755
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling
+ up-regulates img/direct-activation.png ubiquitination IRAK1 0.713
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding IRAK1 0.844
Publications: 1 Organism: Mus Musculus
Pathways:Innate Immune Response, IL1 Signaling , Toll like receptors
+ up-regulates img/direct-activation.png ubiquitination IRAK1 0.77
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding IRAK1 0.792
Publications: 1 Organism: Homo Sapiens
Pathways:IL1 Signaling