8qbn

Structural highlights

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:27098453, PubMed:26895380). 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

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