|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='5sv7' size='340' side='right'caption='[[5sv7]], [[Resolution|resolution]] 3.21Å' scene=''> | | <StructureSection load='5sv7' size='340' side='right'caption='[[5sv7]], [[Resolution|resolution]] 3.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5sv7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SV7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5SV7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5sv7]] is a 4 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=5SV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SV7 FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.209Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5sv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sv7 OCA], [http://pdbe.org/5sv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sv7 RCSB], [http://www.ebi.ac.uk/pdbsum/5sv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sv7 ProSAT]</span></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=5sv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sv7 OCA], [https://pdbe.org/5sv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sv7 RCSB], [https://www.ebi.ac.uk/pdbsum/5sv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sv7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN]] Wolcott-Rallison syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:10932183</ref> | + | [https://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN] Wolcott-Rallison syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:10932183</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN]] Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). | + | [https://www.uniprot.org/uniprot/E2AK3_HUMAN E2AK3_HUMAN] Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]]
| + | [[Category: Li J]] |
| - | [[Category: Li, J]] | + | [[Category: Sha B]] |
| - | [[Category: Sha, B]] | + | [[Category: Wang P]] |
| - | [[Category: Wang, P]] | + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Translation]]
| + | |
| Structural highlights
Disease
E2AK3_HUMAN Wolcott-Rallison syndrome. The disease is caused by mutations affecting the gene represented in this entry.[1]
Function
E2AK3_HUMAN Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity).
Publication Abstract from PubMed
PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ER stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 A resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the beta-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible beta-sandwich domain to recognize and interact with a broad range of misfolded proteins.
The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins.,Wang P, Li J, Sha B Acta Crystallogr D Struct Biol. 2016 Dec 1;72(Pt 12):1290-1297. Epub 2016 Nov 29. PMID:27917829[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Delepine M, Nicolino M, Barrett T, Golamaully M, Lathrop GM, Julier C. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet. 2000 Aug;25(4):406-9. PMID:10932183 doi:http://dx.doi.org/10.1038/78085
- ↑ Wang P, Li J, Sha B. The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins. Acta Crystallogr D Struct Biol. 2016 Dec 1;72(Pt 12):1290-1297. Epub 2016 Nov 29. PMID:27917829 doi:http://dx.doi.org/10.1107/S2059798316018064
|
