View source for 7qwk


==GCN2 (EIF2ALPHA KINASE 4, E2AK4) IN COMPLEX WITH COMPOUND 2==
<StructureSection load='7qwk' size='340' side='right'caption='[[7qwk]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qwk]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QWK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=G41:(2~{S})-~{N}-[(1~{S})-1-[4-[(6-pyridin-4-ylquinazolin-2-yl)amino]phenyl]ethyl]piperidine-2-carboxamide'>G41</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qwk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qwk OCA], [https://pdbe.org/7qwk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qwk RCSB], [https://www.ebi.ac.uk/pdbsum/7qwk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qwk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/E2AK4_HUMAN E2AK4_HUMAN] Pulmonary venoocclusive disease;Pulmonary capillary hemangiomatosis;Heritable pulmonary arterial hypertension. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/E2AK4_HUMAN E2AK4_HUMAN] 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).[UniProtKB:P15442][UniProtKB:Q9QZ05]<ref>PMID:25329545</ref> <ref>PMID:26102367</ref>   (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).<ref>PMID:24310610</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Maia de Oliveira T]]