Tchem IRAK4 Interleukin-1 receptor-associated kinase 4

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 (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. 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 NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Uniprot Accession IDs

• Q9NWZ3
• Q69FE1
• Q8TDF7
• Q9Y589
• IRAK-4

Gene Name

• IRAK4

Ensembl ID

• ENST00000431837
• ENSP00000390327
• ENSG00000198001
• ENST00000440781
• ENSP00000408734
• ENST00000551736
• ENSP00000446490
• ENST00000613694
• ENSP00000479889

Symbol

• IPD1
• REN64
• IRAK-4
• NY-REN-64

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
histone modification site profile	0.87
virus perturbation	0.83
kinase perturbation	0.76
small molecule perturbation	0.69

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Irak Family / Interleukin-1 Receptor-associated Kinase 4

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: 367.33   (req: < 5)

Gene RIFs: 113   (req: <= 3)

Antibodies: 712   (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: 367.33   (req: >= 5)

Gene RIFs: 113   (req: > 3)

Antibodies: 712   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

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

Active Ligands: 1052

Tclin

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

Active Drug: 0