9rsd: Difference between revisions

Latest revision as of 06:27, 8 April 2026

Ternary complex of a charged molecular glue degrader ZZ1-SO2H, BRD4(BD1) neosubstrate, and the CTLH E3 ligase receptor module YPEL5-WDR26

Structural highlights

9rsd is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.38Å
Ligands:	A1IL9, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

WDR26_HUMAN Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

WDR26_HUMAN G-beta-like protein involved in cell signal transduction (PubMed:15378603, PubMed:19446606, PubMed:22065575, PubMed:23625927, PubMed:26895380, PubMed:27098453). Acts as a negative regulator in MAPK signaling pathway (PubMed:15378603). Functions as a scaffolding protein to promote G beta:gamma-mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes (PubMed:22065575, PubMed:23625927). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta-catenin destruction complex, thus negatively regulating CTNNB1 degradation (PubMed:27098453). Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration (PubMed:26895380). Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria (PubMed:19446606). Protects also cells by promoting hypoxia-mediated autophagy and mitophagy (By similarity).[UniProtKB:F1LTR1]^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

References

↑ Zhu Y, Wang Y, Xia C, Li D, Li Y, Zeng W, Yuan W, Liu H, Zhu C, Wu X, Liu M. WDR26: a novel Gbeta-like protein, suppresses MAPK signaling pathway. J Cell Biochem. 2004 Oct 15;93(3):579-87. PMID:15378603 doi:10.1002/jcb.20175
↑ Zhao J, Liu Y, Wei X, Yuan C, Yuan X, Xiao X. A novel WD-40 repeat protein WDR26 suppresses H2O2-induced cell death in neural cells. Neurosci Lett. 2009 Aug 21;460(1):66-71. PMID:19446606 doi:10.1016/j.neulet.2009.05.024
↑ Sun Z, Smrcka AV, Chen S. WDR26 functions as a scaffolding protein to promote Gβγ-mediated phospholipase C β2 (PLCβ2) activation in leukocytes. J Biol Chem. 2013 Jun 7;288(23):16715-16725. PMID:23625927 doi:10.1074/jbc.M113.462564
↑ Ye Y, Tang X, Sun Z, Chen S. Upregulated WDR26 serves as a scaffold to coordinate PI3K/ AKT pathway-driven breast cancer cell growth, migration, and invasion. Oncotarget. 2016 Apr 5;7(14):17854-69. PMID:26895380 doi:10.18632/oncotarget.7439
↑ Goto T, Matsuzawa J, Iemura S, Natsume T, Shibuya H. WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway. FEBS Lett. 2016 May;590(9):1291-303. PMID:27098453 doi:10.1002/1873-3468.12180
↑ Lampert F, Stafa D, Goga A, Soste MV, Gilberto S, Olieric N, Picotti P, Stoffel M, Peter M. The multi-subunit GID/CTLH E3 ubiquitin ligase promotes cell proliferation and targets the transcription factor Hbp1 for degradation. Elife. 2018 Jun 18;7:e35528. PMID:29911972 doi:10.7554/eLife.35528

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Zhu Y, Wang Y, Xia C, Li D, Li Y, Zeng W, Yuan W, Liu H, Zhu C, Wu X, Liu M. WDR26: a novel Gbeta-like protein, suppresses MAPK signaling pathway. J Cell Biochem. 2004 Oct 15;93(3):579-87. PMID:15378603 doi:10.1002/jcb.20175

[2] Zhao J, Liu Y, Wei X, Yuan C, Yuan X, Xiao X. A novel WD-40 repeat protein WDR26 suppresses H2O2-induced cell death in neural cells. Neurosci Lett. 2009 Aug 21;460(1):66-71. PMID:19446606 doi:10.1016/j.neulet.2009.05.024

[3] Sun Z, Smrcka AV, Chen S. WDR26 functions as a scaffolding protein to promote Gβγ-mediated phospholipase C β2 (PLCβ2) activation in leukocytes. J Biol Chem. 2013 Jun 7;288(23):16715-16725. PMID:23625927 doi:10.1074/jbc.M113.462564

[4] Ye Y, Tang X, Sun Z, Chen S. Upregulated WDR26 serves as a scaffold to coordinate PI3K/ AKT pathway-driven breast cancer cell growth, migration, and invasion. Oncotarget. 2016 Apr 5;7(14):17854-69. PMID:26895380 doi:10.18632/oncotarget.7439

[5] Goto T, Matsuzawa J, Iemura S, Natsume T, Shibuya H. WDR26 is a new partner of Axin1 in the canonical Wnt signaling pathway. FEBS Lett. 2016 May;590(9):1291-303. PMID:27098453 doi:10.1002/1873-3468.12180

[6] Lampert F, Stafa D, Goga A, Soste MV, Gilberto S, Olieric N, Picotti P, Stoffel M, Peter M. The multi-subunit GID/CTLH E3 ubiquitin ligase promotes cell proliferation and targets the transcription factor Hbp1 for degradation. Elife. 2018 Jun 18;7:e35528. PMID:29911972 doi:10.7554/eLife.35528

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[2]

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[5]

[6]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9rsd is ON HOLD
+==Ternary complex of a charged molecular glue degrader ZZ1-SO2H, BRD4(BD1) neosubstrate, and the CTLH E3 ligase receptor module YPEL5-WDR26==
+<StructureSection load='9rsd' size='340' side='right'caption='[[9rsd]], [[Resolution|resolution]] 3.38&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9rsd]] 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=9RSD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9RSD FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.38&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IL9:2-chloranyl-4-[[4-[(9~{S})-4,5,13-trimethyl-9-[2-[(2-methylpropan-2-yl)oxy]-2-oxidanylidene-ethyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,7,10,12-pentaen-7-yl]phenyl]carbamoyl]benzenesulfinic+acid'>A1IL9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=9rsd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9rsd OCA], [https://pdbe.org/9rsd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9rsd RCSB], [https://www.ebi.ac.uk/pdbsum/9rsd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9rsd ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/WDR26_HUMAN WDR26_HUMAN] Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/WDR26_HUMAN WDR26_HUMAN] G-beta-like protein involved in cell signal transduction (PubMed:15378603, PubMed:19446606, PubMed:22065575, PubMed:23625927, PubMed:26895380, PubMed:27098453). Acts as a negative regulator in MAPK signaling pathway (PubMed:15378603). Functions as a scaffolding protein to promote G beta:gamma-mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes (PubMed:22065575, PubMed:23625927). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta-catenin destruction complex, thus negatively regulating CTNNB1 degradation (PubMed:27098453). Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration (PubMed:26895380). Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria (PubMed:19446606). Protects also cells by promoting hypoxia-mediated autophagy and mitophagy (By similarity).[UniProtKB:F1LTR1]<ref>PMID:15378603</ref> <ref>PMID:19446606</ref> <ref>PMID:23625927</ref> <ref>PMID:26895380</ref> <ref>PMID:27098453</ref> <ref>PMID:29911972</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chrustowicz J]]
+[[Category: Schulman BA]]

9rsd: Difference between revisions

Latest revision as of 06:27, 8 April 2026

Ternary complex of a charged molecular glue degrader ZZ1-SO2H, BRD4(BD1) neosubstrate, and the CTLH E3 ligase receptor module YPEL5-WDR26

Structural highlights

Disease

Function

References

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