- Protein Name
- Interferon-induced, double-stranded RNA-activated protein kinase
- Gene Name
- EIF2AK2
- Organism
-
Homo sapiens
- Function
- IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MPP |
16 |
5 |
6.0 |
| PIF |
18 |
13 |
15.5 |
| DRS |
3 |
3 |
3.0 |
| MT3 |
9 |
2 |
5.5 |
| AAS |
19 |
7 |
13.0 |
| LBP |
5 |
2 |
3.5 |
| CMP |
3 |
3 |
3.0 |
| PDIG |
18 |
5 |
11.5 |
| ATP |
16 |
6 |
11.0 |
| 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 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
1 |
1 |
0 |
|
2A19
|
16 |
0 |
18 |
3 |
0 |
0 |
0 |
7 |
5 |
3 |
0 |
16 |
0 |
|
2A1A
|
0 |
0 |
13 |
0 |
0 |
0 |
9 |
11 |
2 |
0 |
5 |
0 |
0 |
|
AFP19525
|
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
3UIU
|
6 |
0 |
0 |
0 |
0 |
0 |
0 |
19 |
0 |
0 |
18 |
0 |
0 |