Sde2, N-terminal ubiquitin domain / Yeast Splicing regulator sde2, N-terminal ubiquitin domain / Tuftelin interacting protein, N-terminal domain / Tuftelin interacting protein N terminal / Tetratricopeptide repeat / Sterol biosynthesis ERG24/DHCR-like / Sterol reductase, conserved site / Ergosterol biosynthesis ERG4/ERG24 family / Sterol reductase family signature 1. / Sterol reductase family signature 2. ...Sde2, N-terminal ubiquitin domain / Yeast Splicing regulator sde2, N-terminal ubiquitin domain / Tuftelin interacting protein, N-terminal domain / Tuftelin interacting protein N terminal / Tetratricopeptide repeat / Sterol biosynthesis ERG24/DHCR-like / Sterol reductase, conserved site / Ergosterol biosynthesis ERG4/ERG24 family / Sterol reductase family signature 1. / Sterol reductase family signature 2. / GCF, C-terminal / GC-rich sequence DNA-binding factor-like protein / mRNA splicing factor Cwf18-like / : / TFP11/STIP/Ntr1 / : / cwf18 pre-mRNA splicing factor / Nineteen complex-related protein 2 / Splicing regulator SDE2, SDE2 domain / Cwf19-like protein, C-terminal domain-2 / Cwf19-like, C-terminal domain-1 / Cwf19-like protein / Protein similar to CwfJ C-terminus 2 / Protein similar to CwfJ C-terminus 1 / DHX15, DEXH-box helicase domain / Slt11, RNA recognition motif / Pre-mRNA-splicing factor Cwc2, RNA recognition motif / : / : / Intron-binding protein aquarius, beta-barrel / Intron-binding protein aquarius insert domain / Peptidyl-prolyl cis-trans isomerase E, RNA recognition motif / Pre-mRNA-splicing factor SPF27 / Torus domain / Breast carcinoma amplified sequence 2 (BCAS2) / Torus domain / CWF11 family / Intron-binding protein aquarius, N-terminal / Intron-binding protein aquarius N-terminal / mRNA splicing factor SYF2 / SYF2 splicing factor / G-patch domain / G-patch domain profile. / G-patch domain / glycine rich nucleic binding domain / Pre-mRNA-processing factor 17 / HAT (Half-A-TPR) repeat / Myb-like domain profile. / : / Pre-mRNA-splicing factor 19 / Pre-mRNA-processing factor 19 / Prp19/Pso4-like / Cyclophilin-type peptidyl-prolyl cis-trans isomerase, cyclophilin A-like / BUD31/G10-related, conserved site / G10 protein signature 1. / : / DNA2/NAM7 helicase, helicase domain / : / AAA domain / STL11, N-terminal / SKI-interacting protein SKIP, SNW domain / SKI-interacting protein, SKIP / SKIP/SNW domain / Pre-mRNA-splicing factor Cwf15/Cwc15 / Suppressor of forked / Cwf15/Cwc15 cell cycle control protein / Suppressor of forked protein (Suf) / WD repeat Prp46/PLRG1-like / Pre-mRNA-splicing factor Cwc2/Slt11 / : / G10 protein / Pre-mRNA-splicing factor BUD31 / Pre-mRNA splicing factor component Cdc5p/Cef1, C-terminal / : / : / pre-mRNA splicing factor component / DNA2/NAM7-like helicase / : / Myb-like DNA-binding domain / U2 small nuclear ribonucleoprotein A' / Small nuclear ribonucleoprotein D1 / U-box domain profile. / HIT-like superfamily / Modified RING finger domain / U-box domain / Zinc finger, CCCH-type superfamily / Leucine-rich repeat / : / Helicase associated domain (HA2), ratchet-like / Pre-mRNA-splicing factor Syf1-like / DEAD-box helicase, OB fold / Oligonucleotide/oligosaccharide-binding (OB)-fold / Helicase associated domain (HA2), winged-helix / Helicase-associated domain / Helicase associated domain (HA2) Add an annotation / Anaphase-promoting complex subunit 4, WD40 domain / Small nuclear ribonucleoprotein Sm D3 / Small nuclear ribonucleoprotein Sm D2 / Small nuclear ribonucleoprotein E / Small nuclear ribonucleoprotein G Similarity search - Domain/homology
Sm protein F / RNA helicase / Putative pre-mRNA splicing protein / Uncharacterized protein / Putative cyclophilin protein / Small nuclear ribonucleoprotein Sm D1 / Pre-mRNA-splicing factor PRP46 / Suppressor of forked domain-containing protein / Peptidyl-prolyl cis-trans isomerase / Uncharacterized protein ...Sm protein F / RNA helicase / Putative pre-mRNA splicing protein / Uncharacterized protein / Putative cyclophilin protein / Small nuclear ribonucleoprotein Sm D1 / Pre-mRNA-splicing factor PRP46 / Suppressor of forked domain-containing protein / Peptidyl-prolyl cis-trans isomerase / Uncharacterized protein / G-patch domain-containing protein / Delta(14)-sterol reductase / Putative bud site selection protein / Pre-mRNA-splicing factor SYF2 / Putative pre-mRNA splicing protein / U2 small nuclear ribonucleoprotein A' / Cell cycle control protein / Putative pre-mRNA splicing protein / Putative pre-mRNA splicing protein / Putative pre-mRNA splicing protein / Small nuclear ribonucleoprotein E / Anaphase-promoting complex subunit 4-like WD40 domain-containing protein / U2 small nuclear ribonucleoprotein B'-like protein / Uncharacterized protein / Pre-mRNA-splicing factor SPF27 / Pre-mRNA-processing protein 45 / Pre-mRNA-splicing factor / Pre-mRNA-processing factor 19 / Small nuclear ribonucleoprotein Sm D3 / Sm protein B / Small nuclear ribonucleoprotein G / Nineteen complex-related protein 2-domain-containing protein Similarity search - Component
Journal: Cell Res / Year: 2025 Title: Structural insights into spliceosome fidelity: DHX35-GPATCH1- mediated rejection of aberrant splicing substrates. Authors: Yi Li / Paulina Fischer / Mengjiao Wang / Qianxing Zhou / Aixia Song / Rui Yuan / Wanyu Meng / Fei Xavier Chen / Reinhard Lührmann / Benjamin Lau / Ed Hurt / Jingdong Cheng / Abstract: The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise ...The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise assembly, catalytic splicing and final disassembly of the spliceosome. However, the molecular details of how the spliceosome recognizes and rejects suboptimal splicing substrates remained unclear. Here, we show cryo-electron microscopy structures of spliceosomal quality control complexes from a thermophilic eukaryote, Chaetomium thermophilum. The spliceosomes, henceforth termed B*, are stalled at a catalytically activated state but prior to the first splicing reaction due to an aberrant 5' splice site conformation. This state is recognized by G-patch protein GPATCH1, which is docked onto PRP8-EN and -RH domains and has recruited the cognate DHX35 helicase to its U2 snRNA substrate. In B*, DHX35 has dissociated the U2/branch site helix, while the disassembly helicase DHX15 is docked close to its U6 RNA 3'-end substrate. Our work thus provides mechanistic insights into the concerted action of two spliceosomal helicases in maintaining splicing fidelity by priming spliceosomes that are bound to aberrant splice substrates for disassembly.
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