|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Solution structure of the DSRM domain of Protein activator of the interferon-induced protein kinase== | | ==Solution structure of the DSRM domain of Protein activator of the interferon-induced protein kinase== |
| - | <StructureSection load='2dix' size='340' side='right' caption='[[2dix]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2dix' size='340' side='right'caption='[[2dix]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2dix]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DIX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2dix]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DIX FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKRA, DKFZp564I0123, PACT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2dix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dix OCA], [http://pdbe.org/2dix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2dix RCSB], [http://www.ebi.ac.uk/pdbsum/2dix PDBsum], [http://www.topsan.org/Proteins/RSGI/2dix TOPSAN]</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=2dix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dix OCA], [https://pdbe.org/2dix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dix RCSB], [https://www.ebi.ac.uk/pdbsum/2dix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dix ProSAT], [https://www.topsan.org/Proteins/RSGI/2dix TOPSAN]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PRKRA_HUMAN PRKRA_HUMAN]] Defects in PRKRA are the cause of dystonia type 16 (DYT16) [MIM:[http://omim.org/entry/612067 612067]]. DYT16 is an early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.<ref>PMID:18243799</ref> <ref>PMID:18420150</ref> | + | [https://www.uniprot.org/uniprot/PRKRA_HUMAN PRKRA_HUMAN] Defects in PRKRA are the cause of dystonia type 16 (DYT16) [MIM:[https://omim.org/entry/612067 612067]. DYT16 is an early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.<ref>PMID:18243799</ref> <ref>PMID:18420150</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRKRA_HUMAN PRKRA_HUMAN]] Activates EIF2AK2/PKR in the absence of double stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1.<ref>PMID:9687506</ref> <ref>PMID:10336432</ref> <ref>PMID:11238927</ref> <ref>PMID:16424907</ref> <ref>PMID:16982605</ref> <ref>PMID:17452327</ref> | + | [https://www.uniprot.org/uniprot/PRKRA_HUMAN PRKRA_HUMAN] Activates EIF2AK2/PKR in the absence of double stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1.<ref>PMID:9687506</ref> <ref>PMID:10336432</ref> <ref>PMID:11238927</ref> <ref>PMID:16424907</ref> <ref>PMID:16982605</ref> <ref>PMID:17452327</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/di/2dix_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/di/2dix_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| Line 24: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Dang, W]] | + | [[Category: Large Structures]] |
| - | [[Category: Inoue, M]] | + | [[Category: Dang W]] |
| - | [[Category: Kigawa, T]] | + | [[Category: Inoue M]] |
| - | [[Category: Muto, Y]] | + | [[Category: Kigawa T]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Muto Y]] |
| - | [[Category: Shirouzu, M]] | + | [[Category: Shirouzu M]] |
| - | [[Category: Terada, T]] | + | [[Category: Terada T]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Yokoyama S]] |
| - | [[Category: Dsrm domain]]
| + | |
| - | [[Category: Hypothetical protein prkra]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| Structural highlights
Disease
PRKRA_HUMAN Defects in PRKRA are the cause of dystonia type 16 (DYT16) [MIM:612067. DYT16 is an early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.[1] [2]
Function
PRKRA_HUMAN Activates EIF2AK2/PKR in the absence of double stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1.[3] [4] [5] [6] [7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Camargos S, Scholz S, Simon-Sanchez J, Paisan-Ruiz C, Lewis P, Hernandez D, Ding J, Gibbs JR, Cookson MR, Bras J, Guerreiro R, Oliveira CR, Lees A, Hardy J, Cardoso F, Singleton AB. DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA. Lancet Neurol. 2008 Mar;7(3):207-15. Epub 2008 Feb 1. PMID:18243799 doi:S1474-4422(08)70022-X
- ↑ Seibler P, Djarmati A, Langpap B, Hagenah J, Schmidt A, Bruggemann N, Siebner H, Jabusch HC, Altenmuller E, Munchau A, Lohmann K, Klein C. A heterozygous frameshift mutation in PRKRA (DYT16) associated with generalised dystonia in a German patient. Lancet Neurol. 2008 May;7(5):380-1. doi: 10.1016/S1474-4422(08)70075-9. PMID:18420150 doi:10.1016/S1474-4422(08)70075-9
- ↑ Patel RC, Sen GC. PACT, a protein activator of the interferon-induced protein kinase, PKR. EMBO J. 1998 Aug 3;17(15):4379-90. PMID:9687506 doi:10.1093/emboj/17.15.4379
- ↑ Ito T, Yang M, May WS. RAX, a cellular activator for double-stranded RNA-dependent protein kinase during stress signaling. J Biol Chem. 1999 May 28;274(22):15427-32. PMID:10336432
- ↑ Peters GA, Hartmann R, Qin J, Sen GC. Modular structure of PACT: distinct domains for binding and activating PKR. Mol Cell Biol. 2001 Mar;21(6):1908-20. PMID:11238927 doi:10.1128/MCB.21.6.1908-1920.2001
- ↑ Lee Y, Hur I, Park SY, Kim YK, Suh MR, Kim VN. The role of PACT in the RNA silencing pathway. EMBO J. 2006 Feb 8;25(3):522-32. Epub 2006 Jan 19. PMID:16424907 doi:10.1038/sj.emboj.7600942
- ↑ Peters GA, Li S, Sen GC. Phosphorylation of specific serine residues in the PKR activation domain of PACT is essential for its ability to mediate apoptosis. J Biol Chem. 2006 Nov 17;281(46):35129-36. Epub 2006 Sep 18. PMID:16982605 doi:10.1074/jbc.M607714200
- ↑ Kok KH, Ng MH, Ching YP, Jin DY. Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA. J Biol Chem. 2007 Jun 15;282(24):17649-57. Epub 2007 Apr 23. PMID:17452327 doi:10.1074/jbc.M611768200
|
