GCN2 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. 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. 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. 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. 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. (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. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. Widely expressed (PubMed:10504407). Expressed in lung, smooth muscle cells and macrophages (PubMed:24292273). 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; GCN2 subfamily; Kinase, protein; Other group; PEK family; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor); Translation
Chromosomal Location of Human Ortholog: 15q15.1
Cellular Component:  cytosolic ribosome; polysome
Molecular Function:  ATP binding; eukaryotic translation initiation factor 2alpha kinase activity; protein serine/threonine kinase activity; tRNA binding
Biological Process:  adaptive immune response; cell cycle arrest; cellular response to amino acid starvation; cellular response to cold; cellular response to leucine starvation; cellular response to UV; defense response to virus; DNA damage checkpoint; eiF2alpha phosphorylation in response to endoplasmic reticulum stress; induction by virus of host autophagy; learning; long-term memory; negative regulation by host of viral genome replication; negative regulation of CREB transcription factor activity; negative regulation of neuron differentiation; negative regulation of translational initiation; negative regulation of translational initiation in response to stress; neuron projection extension; positive regulation of adaptive immune response; positive regulation of defense response to virus by host; positive regulation of long-term synaptic potentiation; positive regulation of translational initiation in response to starvation; protein autophosphorylation; protein phosphorylation; regulation of eIF2 alpha phosphorylation by amino acid starvation; regulation of feeding behavior; regulation of translational initiation; regulation of translational initiation by eIF2 alpha phosphorylation; T cell activation involved in immune response; viral translation
Disease: Pulmonary Venoocclusive Disease 2, Autosomal Recessive
Reference #:  Q9P2K8 (UniProtKB)
Alt. Names/Synonyms: E2AK4; eIF-2-alpha kinase GCN2; EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4; Eukaryotic translation initiation factor 2-alpha kinase 4; GCN2; GCN2 eIF2alpha kinase; GCN2-like protein; general control nonderepressible 2; KIAA1338; PVOD2
Gene Symbols: EIF2AK4
Molecular weight: 186,911 Da
Basal Isoelectric point: 5.88  Predict pI for various phosphorylation states
CST Pathways:  Translation: eIF2
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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