Summary

Name EIF2AK4
Full Name eIF-2-alpha kinase GCN2
Synonyms Eukaryotic translation initiation factor 2-alpha kinase 4, GCN2-like protein | GCN2, KIAA1338
Primary ID Q9P2K8
Links - -
Type protein
Relations 4
Function Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity). Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ EIF2AK4down-regulates activity img/direct_inhibition.png phosphorylation EIF2S1 0.915
Publications: 1 Organism: Homo Sapiens
+ EIF2AK4down-regulates img/direct_inhibition.png phosphorylation MARS1 0.2
Publications: 1 Organism: Homo Sapiens
+ DNAJC3down-regulates activity img/direct_inhibition.png binding EIF2AK4 0.577
Publications: 1 Organism: Homo Sapiens
+ EIF2AK4down-regulates activity img/direct_inhibition.png phosphorylation EIF2A 0.484
Publications: 1 Organism: Homo Sapiens