| Structural highlights
7m4o is a 3 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: | X-ray diffraction, Resolution 2.21Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
RN216_HUMAN Cerebellar ataxia-hypogonadism syndrome. The disease is caused by variants affecting the gene represented in this entry.
Function
RN216_HUMAN E3 ubiquitin ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their ubiquitination (PubMed:34998453). Plays a role in the regulation of antiviral responses by promoting the degradation of TRAF3, TLR4 and TLR9 (PubMed:15107846, PubMed:19893624). In turn, down-regulates NF-kappa-B and IRF3 activation as well as beta interferon production. Participates also in the regulation of autophagy by ubiquitinating BECN1 leading to its degradation and autophagy inhibition (PubMed:25484083). Plays a role in ARC-dependent synaptic plasticity by mediating ARC ubiquitination resulting in its rapid proteasomal degradation (PubMed:24945773). Plays aso an essential role in spermatogenesis and male fertility (By similarity). Mechanistically, regulates meiosis by promoting the degradation of PRKACB through the ubiquitin-mediated lysosome pathway (By similarity). Modulates the gonadotropin-releasing hormone signal pathway by affecting the stability of STAU2 that is required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite (By similarity).[UniProtKB:P58283][1] [2] [3] [4] [5] Inhibits TNF and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP mediated apoptosis.[6]
See Also
References
- ↑ Chuang TH, Ulevitch RJ. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat Immunol. 2004 May;5(5):495-502. doi: 10.1038/ni1066. Epub 2004 Apr 25. PMID:15107846 doi:http://dx.doi.org/10.1038/ni1066
- ↑ Nakhaei P, Mesplede T, Solis M, Sun Q, Zhao T, Yang L, Chuang TH, Ware CF, Lin R, Hiscott J. The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation. PLoS Pathog. 2009 Nov;5(11):e1000650. doi: 10.1371/journal.ppat.1000650. Epub , 2009 Nov 6. PMID:19893624 doi:http://dx.doi.org/10.1371/journal.ppat.1000650
- ↑ Mabb AM, Je HS, Wall MJ, Robinson CG, Larsen RS, Qiang Y, Corrêa SA, Ehlers MD. Triad3A regulates synaptic strength by ubiquitination of Arc. Neuron. 2014 Jun 18;82(6):1299-316. PMID:24945773 doi:10.1016/j.neuron.2014.05.016
- ↑ Xu C, Feng K, Zhao X, Huang S, Cheng Y, Qian L, Wang Y, Sun H, Jin M, Chuang TH, Zhang Y. Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination. Autophagy. 2014;10(12):2239-50. PMID:25484083 doi:10.4161/15548627.2014.981792
- ↑ Cotton TR, Cobbold SA, Bernardini JP, Richardson LW, Wang XS, Lechtenberg BC. Structural basis of K63-ubiquitin chain formation by the Gordon-Holmes syndrome RBR E3 ubiquitin ligase RNF216. Mol Cell. 2022 Feb 3;82(3):598-615.e8. PMID:34998453 doi:10.1016/j.molcel.2021.12.005
- ↑ Chen D, Li X, Zhai Z, Shu HB. A novel zinc finger protein interacts with receptor-interacting protein (RIP) and J Biol Chem. 2002 May 3;277(18):15985-91. PMID:11854271 doi:10.1074/jbc.M108675200
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