Tchem IRAK1 Interleukin-1 receptor-associated kinase 1

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• P51617
• D3DWW3
• D3DWW4
• Q7Z5V4
• Q96C06
• Q96RL2
• IRAK-1

Gene Name

• IRAK1

Ensembl ID

• ENST00000369974
• ENSP00000358991
• ENSG00000184216
• ENST00000369980
• ENSP00000358997
• ENST00000393687
• ENSP00000377291

Symbol

• IRAK
• IRAK
• pelle

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
biological process	0.99
hub protein	0.98
transcription factor perturbation	0.94
small molecule	0.92

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Irak Family / Interleukin-1 Receptor-associated Kinase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 642.82   (req: < 5)

Gene RIFs: 180   (req: <= 3)

Antibodies: 954   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 642.82   (req: >= 5)

Gene RIFs: 180   (req: > 3)

Antibodies: 954   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 42

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 31

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2