- Function
- Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/SUI2) on 'Ser-52' in response to low amino acid availability (PubMed:1739968, PubMed:7623840, PubMed:8798780, PubMed:9528799, PubMed:10983975, PubMed:17202131). Plays a role as an activator of the general amino acid control (GAAC) pathway required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/SUI2 either to a competitive inhibitor of translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator GCN4, and hence allowing GCN4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:2660141, PubMed:2188100, PubMed:1739968, PubMed:7621831, PubMed:7623840, PubMed:8798780, PubMed:10801780, PubMed:11350982, PubMed:24333428). Binds uncharged tRNAs (PubMed:7623840, PubMed:10983975).
(orthologuous-specific) Binds to aminoacylated tRNA(Phe) less tightly than to deacylated tRNA(Phe) (PubMed:10983975). Binds to double-stranded RNA (PubMed:9430731).
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MPP |
8 |
8 |
8.0 |
| DFG |
23 |
23 |
23.0 |
| PIF |
18 |
18 |
18.0 |
| DRS |
21 |
4 |
11.0 |
| MT3 |
16 |
7 |
12.0 |
| PDIG |
18 |
16 |
17.0 |
| ATP |
18 |
7 |
17.5 |
| 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 |
0 |
1 |
1 |
2 |
0 |
0 |
1 |
0 |
0 |
0 |
2 |
5 |
0 |
|
1ZY5
|
0 |
0 |
0 |
0 |
0 |
0 |
15 |
0 |
0 |
0 |
0 |
17 |
0 |
|
AFP15442
|
0 |
23 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1ZYD
|
0 |
0 |
0 |
11 |
0 |
0 |
7 |
0 |
0 |
0 |
18 |
18 |
0 |
|
1ZY4
|
8 |
0 |
0 |
21 |
0 |
0 |
12 |
0 |
0 |
0 |
16 |
18 |
0 |
|
1ZXE
|
0 |
0 |
18 |
17 |
0 |
0 |
11 |
0 |
0 |
0 |
0 |
17 |
0 |
|
1ZYC
|
0 |
0 |
0 |
5 |
0 |
0 |
16 |
0 |
0 |
0 |
0 |
18 |
0 |