6wnx

Structural highlights

Disease

FBW1B_HUMAN Non-specific syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Function

FBW1B_HUMAN Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. SCF(FBXW11) mediates the ubiquitination of phosphorylated CTNNB1 and participates in Wnt signaling regulation. SCF(FBXW11) mediates the ubiquitination of phosphorylated NFKBIA, which degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. SCF(FBXW11) mediates the ubiquitination of IFNAR1. SCF(FBXW11) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25503564). Involved in the oxidative stress-induced a ubiquitin-mediated decrease in RCAN1. Mediates the degradation of CDC25A induced by ionizing radiation in cells progressing through S phase and thus may function in the intra-S-phase checkpoint. Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and phosphorylated PER2. SCF(FBXW11) mediates the ubiquitination of CYTH1, and probably CYTH2 (PubMed:29420262).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]} (Microbial infection) Target of human immunodeficiency virus type 1 (HIV-1) protein VPU to polyubiquitinate and deplete BST2 from cells and antagonize its antiviral action.^[13]

References

1. ↑ Fuchs SY, Chen A, Xiong Y, Pan ZQ, Ronai Z. HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene. 1999 Mar 25;18(12):2039-46. PMID:10321728 doi:10.1038/sj.onc.1202760
2. ↑ Vuillard L, Nicholson J, Hay RT. A complex containing betaTrCP recruits Cdc34 to catalyse ubiquitination of IkappaBalpha. FEBS Lett. 1999 Jul 23;455(3):311-4. PMID:10437795 doi:10.1016/s0014-5793(99)00895-9
3. ↑ Suzuki H, Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M, Furuichi K, Shikama H, Tanaka K. Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination. J Biol Chem. 2000 Jan 28;275(4):2877-84. PMID:10644755
4. ↑ Wu K, Fuchs SY, Chen A, Tan P, Gomez C, Ronai Z, Pan ZQ. The SCF(HOS/beta-TRCP)-ROC1 E3 ubiquitin ligase utilizes two distinct domains within CUL1 for substrate targeting and ubiquitin ligation. Mol Cell Biol. 2000 Feb;20(4):1382-93. PMID:10648623 doi:10.1128/MCB.20.4.1382-1393.2000
5. ↑ Kumar KG, Tang W, Ravindranath AK, Clark WA, Croze E, Fuchs SY. SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor. EMBO J. 2003 Oct 15;22(20):5480-90. PMID:14532120 doi:10.1093/emboj/cdg524
6. ↑ Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature. 2003 Nov 6;426(6962):87-91. PMID:14603323 doi:10.1038/nature02082
7. ↑ Shirogane T, Jin J, Ang XL, Harper JW. SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem. 2005 Jul 22;280(29):26863-72. Epub 2005 May 24. PMID:15917222 doi:http://dx.doi.org/10.1074/jbc.M502862200
8. ↑ Asada S, Ikeda A, Nagao R, Hama H, Sudo T, Fukamizu A, Kasuya Y, Kishi T. Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFbeta-TrCP ubiquitin ligase. Int J Mol Med. 2008 Jul;22(1):95-104 PMID:18575781
9. ↑ Peschiaroli A, Skaar JR, Pagano M, Melino G. The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor regulating cell survival. Oncogene. 2010 Mar 4;29(9):1384-93. PMID:19966869 doi:10.1038/onc.2009.430
10. ↑ Wu K, Kovacev J, Pan ZQ. Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for polyubiquitination on a SCF substrate. Mol Cell. 2010 Mar 26;37(6):784-96. doi: 10.1016/j.molcel.2010.02.025. PMID:20347421 doi:10.1016/j.molcel.2010.02.025
11. ↑ Pagan JK, Marzio A, Jones MJ, Saraf A, Jallepalli PV, Florens L, Washburn MP, Pagano M. Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nat Cell Biol. 2015 Jan;17(1):31-43. PMID:25503564 doi:10.1038/ncb3076
12. ↑ Mohanan V, Nakata T, Desch AN, Lévesque C, Boroughs A, Guzman G, Cao Z, Creasey E, Yao J, Boucher G, Charron G, Bhan AK, Schenone M, Carr SA, Reinecker HC, Daly MJ, Rioux JD, Lassen KG, Xavier RJ. C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science. 2018 Mar 9;359(6380):1161-1166. PMID:29420262 doi:10.1126/science.aan0814
13. ↑ Mangeat B, Gers-Huber G, Lehmann M, Zufferey M, Luban J, Piguet V. HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog. 2009 Sep;5(9):e1000574. PMID:19730691 doi:10.1371/journal.ppat.1000574