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| | <SX load='5xjc' size='340' side='right' viewer='molstar' caption='[[5xjc]], [[Resolution|resolution]] 3.60Å' scene=''> | | <SX load='5xjc' size='340' side='right' viewer='molstar' caption='[[5xjc]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xjc]] is a 50 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XJC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XJC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xjc]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_adenovirus_2 Human adenovirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XJC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </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=5xjc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjc OCA], [https://pdbe.org/5xjc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xjc RCSB], [https://www.ebi.ac.uk/pdbsum/5xjc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjc ProSAT]</span></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=5xjc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjc OCA], [http://pdbe.org/5xjc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xjc RCSB], [http://www.ebi.ac.uk/pdbsum/5xjc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN]] Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:[http://omim.org/entry/600059 600059]]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP13 inheritance is autosomal dominant.<ref>PMID:17317632</ref> <ref>PMID:11468273</ref> [:]<ref>PMID:11910553</ref> <ref>PMID:12714658</ref> [[http://www.uniprot.org/uniprot/U5S1_HUMAN U5S1_HUMAN]] Mandibulofacial dysostosis-microcephaly syndrome. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/CDC5L_HUMAN CDC5L_HUMAN]] Note=A chromosomal aberration involving CDC5L is found in multicystic renal dysplasia. Translocation t(6;19)(p21;q13.1) with USF2. [[http://www.uniprot.org/uniprot/U520_HUMAN U520_HUMAN]] Retinitis pigmentosa. Retinitis pigmentosa 33 (RP33) [MIM:[http://omim.org/entry/610359 610359]]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:16723661</ref> <ref>PMID:23045696</ref> <ref>PMID:19878916</ref> <ref>PMID:19710410</ref> <ref>PMID:21618346</ref> | + | [https://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN] Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:[https://omim.org/entry/600059 600059]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP13 inheritance is autosomal dominant.<ref>PMID:17317632</ref> <ref>PMID:11468273</ref> [:]<ref>PMID:11910553</ref> <ref>PMID:12714658</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RUXG_HUMAN RUXG_HUMAN]] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [[http://www.uniprot.org/uniprot/RUXE_HUMAN RUXE_HUMAN]] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [[http://www.uniprot.org/uniprot/SRRM2_HUMAN SRRM2_HUMAN]] Involved in pre-mRNA splicing. May function at or prior to the first catalytic step of splicing at the catalytic center of the spliceosome. May do so by stabilizing the catalytic center or the position of the RNA substrate (By similarity). Binds to RNA.<ref>PMID:10668804</ref> [[http://www.uniprot.org/uniprot/SLU7_HUMAN SLU7_HUMAN]] Participates in the second catalytic step of pre-mRNA splicing, when the free hydroxyl group of exon I attacks the 3'-splice site to generate spliced mRNA and the excised lariat intron. Required for holding exon 1 properly in the spliceosome and for correct AG identification when more than one possible AG exists in 3'-splicing site region. May be involved in the activation of proximal AG. Probably also involved in alternative splicing regulation.<ref>PMID:10197984</ref> <ref>PMID:10647016</ref> <ref>PMID:12764196</ref> <ref>PMID:15728250</ref> [[http://www.uniprot.org/uniprot/AQR_HUMAN AQR_HUMAN]] Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis. Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly. May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing.<ref>PMID:16949364</ref> [[http://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN]] Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes. [[http://www.uniprot.org/uniprot/SNW1_HUMAN SNW1_HUMAN]] Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. Functions as a splicing factor in pre-mRNA splicing. Is required in the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. Is proposed to recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA.<ref>PMID:10644367</ref> <ref>PMID:11278756</ref> <ref>PMID:11371506</ref> <ref>PMID:11514567</ref> <ref>PMID:12840015</ref> <ref>PMID:14985122</ref> <ref>PMID:15194481</ref> <ref>PMID:15905409</ref> <ref>PMID:18794151</ref> <ref>PMID:19818711</ref> <ref>PMID:21245387</ref> <ref>PMID:21460037</ref> <ref>PMID:9632709</ref> [[http://www.uniprot.org/uniprot/SMD2_HUMAN SMD2_HUMAN]] Required for pre-mRNA splicing. Required for snRNP biogenesis (By similarity). [[http://www.uniprot.org/uniprot/CWC15_HUMAN CWC15_HUMAN]] Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing.<ref>PMID:20176811</ref> [[http://www.uniprot.org/uniprot/SMD3_HUMAN SMD3_HUMAN]] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner.<ref>PMID:11574479</ref> [[http://www.uniprot.org/uniprot/DHX8_HUMAN DHX8_HUMAN]] Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.<ref>PMID:8608946</ref> [[http://www.uniprot.org/uniprot/RSMB_HUMAN RSMB_HUMAN]] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. May have a functional role in the pre-mRNA splicing or in snRNP structure. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner (By similarity). [[http://www.uniprot.org/uniprot/CASC3_HUMAN CASC3_HUMAN]] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons (By similarity). May play a role in mRNA transport (By similarity). Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer.<ref>PMID:17652158</ref> <ref>PMID:17375189</ref> [[http://www.uniprot.org/uniprot/PLRG1_HUMAN PLRG1_HUMAN]] Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. [[http://www.uniprot.org/uniprot/PKRI1_HUMAN PKRI1_HUMAN]] Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity (By similarity). [[http://www.uniprot.org/uniprot/CRNL1_HUMAN CRNL1_HUMAN]] Involved in pre-mRNA splicing process. [[http://www.uniprot.org/uniprot/RUXF_HUMAN RUXF_HUMAN]] Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing. Associated with snRNP U1, U2, U4/U6 and U5. [[http://www.uniprot.org/uniprot/RU2B_HUMAN RU2B_HUMAN]] Involved in pre-mRNA splicing. This protein is associated with snRNP U2. It binds stem loop IV of U2 snRNA only in presence of the U2A' protein. [[http://www.uniprot.org/uniprot/SPF27_HUMAN SPF27_HUMAN]] Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR).<ref>PMID:24332808</ref> [[http://www.uniprot.org/uniprot/CWC22_HUMAN CWC22_HUMAN]] Required for pre-mRNA splicing and for exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.<ref>PMID:22959432</ref> <ref>PMID:22961380</ref> <ref>PMID:23236153</ref> [[http://www.uniprot.org/uniprot/SYF2_HUMAN SYF2_HUMAN]] May be involved in pre-mRNA splicing. [[http://www.uniprot.org/uniprot/PRP17_HUMAN PRP17_HUMAN]] Associates with the spliceosome late in the splicing pathway and may function in the second step of pre-mRNA splicing.<ref>PMID:9830021</ref> [[http://www.uniprot.org/uniprot/SMD1_HUMAN SMD1_HUMAN]] May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through nonspecific electrostatic contacts with RNA. [[http://www.uniprot.org/uniprot/RBM8A_HUMAN RBM8A_HUMAN]] Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The heterodimer MAGOH-RBM8A interacts with PYM that function to enhance the translation of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Remains associated with mRNAs in the cytoplasm until the mRNAs engage the translation machinery. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Complex with MAGOH is a component of the nonsense mediated decay (NMD) pathway.<ref>PMID:12121612</ref> <ref>PMID:12718880</ref> <ref>PMID:12730685</ref> <ref>PMID:16209946</ref> <ref>PMID:19409878</ref> [[http://www.uniprot.org/uniprot/PRP19_HUMAN PRP19_HUMAN]] Plays a role in DNA double-strand break (DSB) repair. Binds double-stranded DNA in a sequence-nonspecific manner. Acts as a structural component of the nuclear framework. May also serve as a support for spliceosome binding and activity. Essential for spliceosome assembly in a oligomerization-dependent manner and might also be important for spliceosome stability. May have E3 ubiquitin ligase activity. The PSO4 complex is required in the DNA interstrand cross-links (ICLs) repair process. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing.<ref>PMID:11082287</ref> <ref>PMID:12960389</ref> <ref>PMID:16332694</ref> <ref>PMID:15660529</ref> <ref>PMID:16223718</ref> <ref>PMID:16388800</ref> [[http://www.uniprot.org/uniprot/U5S1_HUMAN U5S1_HUMAN]] Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex required for pre-mRNA splicing. Binds GTP. [[http://www.uniprot.org/uniprot/SYF1_HUMAN SYF1_HUMAN]] Involved in transcription-coupled repair (TCR), transcription and pre-mRNA splicing.<ref>PMID:10944529</ref> <ref>PMID:17981804</ref> [[http://www.uniprot.org/uniprot/CDC5L_HUMAN CDC5L_HUMAN]] DNA-binding protein involved in cell cycle control. May act as a transcription activator. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing.<ref>PMID:9038199</ref> <ref>PMID:9632794</ref> <ref>PMID:9468527</ref> <ref>PMID:10570151</ref> <ref>PMID:11101529</ref> <ref>PMID:11082045</ref> <ref>PMID:11544257</ref> <ref>PMID:12927788</ref> <ref>PMID:18583928</ref> [[http://www.uniprot.org/uniprot/RBM22_HUMAN RBM22_HUMAN]] Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.<ref>PMID:17045351</ref> <ref>PMID:21122810</ref> <ref>PMID:22246180</ref> [[http://www.uniprot.org/uniprot/MGN2_HUMAN MGN2_HUMAN]] Involved in mRNA splicing and in the nonsense-mediated decay (NMD) pathway. [[http://www.uniprot.org/uniprot/U520_HUMAN U520_HUMAN]] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.<ref>PMID:16723661</ref> <ref>PMID:8670905</ref> <ref>PMID:9539711</ref> <ref>PMID:23045696</ref> [[http://www.uniprot.org/uniprot/RU2A_HUMAN RU2A_HUMAN]] This protein is associated with sn-RNP U2. It helps the A' protein to bind stem loop IV of U2 snRNA. [[http://www.uniprot.org/uniprot/IF4A3_HUMAN IF4A3_HUMAN]] ATP-dependent RNA helicase. Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Constitutes at least part of the platform anchoring other EJC proteins to spliced mRNAs. Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH/RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH/RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed.<ref>PMID:15034551</ref> <ref>PMID:16209946</ref> <ref>PMID:16170325</ref> <ref>PMID:17375189</ref> <ref>PMID:19409878</ref> [[http://www.uniprot.org/uniprot/PPIL1_HUMAN PPIL1_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. May be involved in pre-mRNA splicing.<ref>PMID:16595688</ref> [[http://www.uniprot.org/uniprot/SNR40_HUMAN SNR40_HUMAN]] Component of the U5 small nuclear ribonucleoprotein (snRNP) complex. The U5 snRNP is part of the spliceosome, a multiprotein complex that catalyzes the removal of introns from pre-messenger RNAs.<ref>PMID:9774689</ref>
| + | [https://www.uniprot.org/uniprot/PRP8_HUMAN PRP8_HUMAN] Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 21: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5xjc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5xjc" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| | + | *[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] |
| | + | *[[Sm-like protein 3D structures|Sm-like protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 27: |
Line 31: |
| | </SX> | | </SX> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | + | [[Category: Human adenovirus 2]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RNA helicase]]
| + | [[Category: Finci IL]] |
| - | [[Category: Finci, I L]] | + | [[Category: Hang J]] |
| - | [[Category: Hang, J]] | + | [[Category: Lei J]] |
| - | [[Category: Lei, J]] | + | [[Category: Shi Y]] |
| - | [[Category: Shi, Y]] | + | [[Category: Yan C]] |
| - | [[Category: Yan, C]] | + | [[Category: Zhang X]] |
| - | [[Category: Zhang, X]] | + | |
| - | [[Category: Atomic structure]]
| + | |
| - | [[Category: C* complex]]
| + | |
| - | [[Category: Ejc]]
| + | |
| - | [[Category: Human spliceosome]]
| + | |
| - | [[Category: Rna splicing]]
| + | |
| - | [[Category: Splicing]]
| + | |
| - | [[Category: Step 2 factor]]
| + | |
| Structural highlights
Disease
PRP8_HUMAN Defects in PRPF8 are the cause of retinitis pigmentosa type 13 (RP13) [MIM:600059. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP13 inheritance is autosomal dominant.[1] [2] [:][3] [4]
Function
PRP8_HUMAN Central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. Interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes.
Publication Abstract from PubMed
Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C * complex) at an average resolution of 3.76 A. The splicing factor Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an extended conformation, binds Prp8 and Cwc22, and is poised for selection of the 3'-splice site. Remarkably, the intron lariat traverses through a positively charged central channel of RBM22; this unusual organization suggests mechanisms of intron recruitment, confinement, and release. The protein PRKRIP1 forms a 100-A alpha helix linking the distant U2 snRNP to the catalytic center. A 35-residue fragment of the ATPase/helicase Prp22 latches onto Prp8, and the quaternary exon junction complex (EJC) recognizes upstream 5'-exon sequences and associates with Cwc22 and the GTPase Snu114. These structural features reveal important mechanistic insights into exon ligation.
An Atomic Structure of the Human Spliceosome.,Zhang X, Yan C, Hang J, Finci LI, Lei J, Shi Y Cell. 2017 May 18;169(5):918-929.e14. doi: 10.1016/j.cell.2017.04.033. Epub 2017 , May 11. PMID:28502770[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pena V, Liu S, Bujnicki JM, Luhrmann R, Wahl MC. Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa. Mol Cell. 2007 Feb 23;25(4):615-24. PMID:17317632 doi:10.1016/j.molcel.2007.01.023
- ↑ McKie AB, McHale JC, Keen TJ, Tarttelin EE, Goliath R, van Lith-Verhoeven JJ, Greenberg J, Ramesar RS, Hoyng CB, Cremers FP, Mackey DA, Bhattacharya SS, Bird AC, Markham AF, Inglehearn CF. Mutations in the pre-mRNA splicing factor gene PRPC8 in autosomal dominant retinitis pigmentosa (RP13). Hum Mol Genet. 2001 Jul 15;10(15):1555-62. PMID:11468273
- ↑ van Lith-Verhoeven JJ, van der Velde-Visser SD, Sohocki MM, Deutman AF, Brink HM, Cremers FP, Hoyng CB. Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13). Ophthalmic Genet. 2002 Mar;23(1):1-12. PMID:11910553
- ↑ Martinez-Gimeno M, Gamundi MJ, Hernan I, Maseras M, Milla E, Ayuso C, Garcia-Sandoval B, Beneyto M, Vilela C, Baiget M, Antinolo G, Carballo M. Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2003 May;44(5):2171-7. PMID:12714658
- ↑ Zhang X, Yan C, Hang J, Finci LI, Lei J, Shi Y. An Atomic Structure of the Human Spliceosome. Cell. 2017 May 18;169(5):918-929.e14. doi: 10.1016/j.cell.2017.04.033. Epub 2017 , May 11. PMID:28502770 doi:http://dx.doi.org/10.1016/j.cell.2017.04.033
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