Tchem EIF2AK4 eIF-2-alpha kinase GCN2

Protein Summary

Description

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52' in response to low amino acid availability (PubMed:25329545). Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation. Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the 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 ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion. 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. Plays a role in neurite outgrowth inhibition. Plays a proapoptotic role in response to glucose deprivation. 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). (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]

Uniprot Accession IDs

• Q9P2K8
• C9JEC4
• Q69YL7
• Q6DC97
• Q96GN6
• Q9H5K1
• Q9NSQ3
• Q9NSZ5
• Q9UJ56

Gene Name

• EIF2AK4

Ensembl ID

• ENST00000263791
• ENSP00000263791
• ENSG00000128829
• ENST00000559624
• ENSP00000453148

Symbol

• GCN2
• KIAA1338
• GCN2
• PVOD2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
hub protein	0.94
molecular function	0.91
histone modification site profile	0.79
interacting protein	0.69

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Eif-2-alpha Kinase Gcn2

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Pek Family / Gcn2 Subfamily / Eukaryotic Translation Initiation Factor 2-alpha 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: 543.89   (req: < 5)

Gene RIFs: 74   (req: <= 3)

Antibodies: 377   (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: 543.89   (req: >= 5)

Gene RIFs: 74   (req: > 3)

Antibodies: 377   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 35

Tchem

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

Active Ligands: 9

Tclin

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

Active Drug: 1