2dix

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

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ 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
8. ↑ 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