- Protein Name
- Interleukin-1 receptor-associated kinase 4
- Gene Name
- IRAK4
- Organism
-
Homo sapiens
- 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 (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.
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MPP |
21 |
2 |
16.0 |
| DFG |
22 |
2 |
9.0 |
| PIF |
11 |
11 |
11.0 |
| DRS |
11 |
5 |
7.0 |
| EDI |
4 |
2 |
2.0 |
| MT3 |
25 |
2 |
9.0 |
| AAS |
20 |
4 |
15.0 |
| CMP |
4 |
2 |
2.5 |
| ATP |
32 |
1 |
10.0 |
| PDB ID |
Maximum Consensus Site Population |
| MPP site |
DFG site |
PIF site |
DRS site |
DEF site |
EDI site |
MT3 site |
AAS site |
LBP site |
CMP site |
PDIG site |
ATP site |
PMP site |
| Total Druggable Structures per Site |
13 |
5 |
0 |
0 |
0 |
0 |
4 |
10 |
0 |
0 |
0 |
11 |
0 |
|
2O8Y
|
19 |
4 |
11 |
10 |
0 |
2 |
4 |
12 |
0 |
4 |
0 |
22 |
0 |
|
4U97
|
21 |
0 |
0 |
10 |
0 |
0 |
5 |
15 |
0 |
0 |
0 |
18 |
0 |
|
4Y73
|
18 |
9 |
0 |
0 |
0 |
0 |
14 |
16 |
0 |
0 |
0 |
13 |
0 |
|
4YP8
|
2 |
17 |
0 |
0 |
0 |
0 |
0 |
15 |
0 |
0 |
0 |
16 |
0 |
|
4ZTL
|
0 |
15 |
0 |
0 |
0 |
0 |
0 |
16 |
0 |
0 |
0 |
14 |
0 |
|
4U9A
|
20 |
0 |
0 |
6 |
0 |
0 |
6 |
16 |
0 |
0 |
0 |
20 |
0 |
|
2OIB
|
19 |
12 |
0 |
10 |
0 |
0 |
20 |
18 |
0 |
0 |
0 |
20 |
0 |
|
4RMZ
|
18 |
9 |
0 |
5 |
0 |
0 |
20 |
10 |
0 |
0 |
0 |
16 |
0 |
|
2OIC
|
19 |
18 |
0 |
11 |
0 |
2 |
25 |
17 |
0 |
3 |
0 |
27 |
0 |
|
2OID
|
17 |
21 |
0 |
8 |
0 |
0 |
9 |
20 |
0 |
2 |
0 |
24 |
0 |
|
2NRU
|
20 |
22 |
0 |
7 |
0 |
0 |
18 |
15 |
0 |
0 |
0 |
21 |
0 |
|
4ZTM
|
17 |
4 |
0 |
0 |
0 |
0 |
0 |
13 |
0 |
0 |
0 |
13 |
0 |
|
2NRY
|
18 |
17 |
0 |
9 |
0 |
4 |
15 |
17 |
0 |
2 |
0 |
32 |
0 |
|
AFQ9NWZ3
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4YO6
|
20 |
14 |
0 |
0 |
0 |
0 |
8 |
16 |
0 |
0 |
0 |
13 |
0 |
|
4XS2
|
14 |
0 |
0 |
0 |
0 |
0 |
2 |
16 |
0 |
0 |
0 |
19 |
0 |
|
4ZTN
|
18 |
11 |
0 |
0 |
0 |
0 |
8 |
18 |
0 |
0 |
0 |
14 |
0 |