ID FBW1B_HUMAN Reviewed; 542 AA. AC Q9UKB1; B2RC98; Q9P2S8; Q9P2S9; Q9Y4C6; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 217. DE RecName: Full=F-box/WD repeat-containing protein 11; DE AltName: Full=F-box and WD repeats protein beta-TrCP2 {ECO:0000303|PubMed:10694485}; DE AltName: Full=F-box/WD repeat-containing protein 1B; DE AltName: Full=Homologous to Slimb protein {ECO:0000303|PubMed:10321728}; DE Short=HOS {ECO:0000303|PubMed:10321728}; GN Name=FBXW11 {ECO:0000303|PubMed:26837067, GN ECO:0000312|HGNC:HGNC:13607}; GN Synonyms=BTRCP2 {ECO:0000303|PubMed:10694485}, FBW1B, FBXW1B, KIAA0696 GN {ECO:0000303|PubMed:9734811}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2; RA Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., RA Pagano M.; RT "Identification of a family of human F-box proteins."; RL Curr. Biol. 9:1177-1179(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING. RC TISSUE=Fetal lung; RX PubMed=10694485; DOI=10.1006/bbrc.2000.2241; RA Koike J., Sagara N., Kirikoshi H., Takagi A., Miwa T., Hirai M., Katoh M.; RT "Molecular cloning and genomic structure of the betaTRCP2 gene on RT chromosome 5q35.1."; RL Biochem. Biophys. Res. Commun. 269:103-109(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. The RT complete sequences of 100 new cDNA clones from brain which can code for RT large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP IDENTIFICATION IN THE SCF(FBXW11) COMPLEX. RX PubMed=10066435; DOI=10.1006/bbrc.1999.0289; RA Suzuki H., Chiba T., Kobayashi M., Takeuchi M., Suzuki T., Ichiyama A., RA Ikenoue T., Omata M., Furuichi K., Tanaka K.; RT "IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing RT Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and RT betaTrCP2."; RL Biochem. Biophys. Res. Commun. 256:127-132(1999). RN [7] RP FUNCTION IN UBIQUITINATION OF NFKBIA AND CTNNB1, AND PATHWAY. RX PubMed=10321728; DOI=10.1038/sj.onc.1202760; RA Fuchs S.Y., Chen A., Xiong Y., Pan Z.Q., Ronai Z.; RT "HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 RT and targets the phosphorylation-dependent degradation of IkappaB and beta- RT catenin."; RL Oncogene 18:2039-2046(1999). RN [8] RP SELF-ASSOCIATION, FUNCTION IN UBIQUITINATION OF NFKBIA, AND PATHWAY. RX PubMed=10644755; DOI=10.1074/jbc.275.4.2877; RA Suzuki H., Chiba T., Suzuki T., Fujita T., Ikenoue T., Omata M., RA Furuichi K., Shikama H., Tanaka K.; RT "Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to RT IkappaBalpha for signal-dependent ubiquitination."; RL J. Biol. Chem. 275:2877-2884(2000). RN [9] RP FUNCTION IN IFNAR1 UBIQUITINATION, AND PATHWAY. RX PubMed=14532120; DOI=10.1093/emboj/cdg524; RA Kumar K.G., Tang W., Ravindranath A.K., Clark W.A., Croze E., Fuchs S.Y.; RT "SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of RT the interferon-alpha receptor."; RL EMBO J. 22:5480-5490(2003). RN [10] RP IDENTIFICATION IN THE SCF(FBXW11) COMPLEX, I, FUNCTION IN UBIQUITINATION OF RP NFKBIA, AND PATHWAY. RX PubMed=10437795; DOI=10.1016/s0014-5793(99)00895-9; RA Vuillard L., Nicholson J., Hay R.T.; RT "A complex containing betaTrCP recruits Cdc34 to catalyse ubiquitination of RT IkappaBalpha."; RL FEBS Lett. 455:311-314(1999). RN [11] RP FUNCTION, AND PATHWAY. RX PubMed=11158290; DOI=10.1128/mcb.21.4.1024-1035.2001; RA Heissmeyer V., Krappmann D., Hatada E.N., Scheidereit C.; RT "Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated RT ubiquitination and degradation for the NF-kappaB precursor p105 and RT IkappaBalpha."; RL Mol. Cell. Biol. 21:1024-1035(2001). RN [12] RP FUNCTION. RX PubMed=15337770; DOI=10.1074/jbc.m407082200; RA Kumar K.G., Krolewski J.J., Fuchs S.Y.; RT "Phosphorylation and specific ubiquitin acceptor sites are required for RT ubiquitination and degradation of the IFNAR1 subunit of type I interferon RT receptor."; RL J. Biol. Chem. 279:46614-46620(2004). RN [13] RP INTERACTION WITH TRIM21. RX PubMed=16880511; DOI=10.1128/mcb.01630-05; RA Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M., RA Krek W.; RT "Regulation of p27 degradation and S-phase progression by Ro52 RING finger RT protein."; RL Mol. Cell. Biol. 26:5994-6004(2006). RN [14] RP FUNCTION OF THE SCF(FBXW11) COMPLEX. RX PubMed=10648623; DOI=10.1128/mcb.20.4.1382-1393.2000; RA Wu K., Fuchs S.Y., Chen A., Tan P., Gomez C., Ronai Z., Pan Z.Q.; RT "The SCF(HOS/beta-TRCP)-ROC1 E3 ubiquitin ligase utilizes two distinct RT domains within CUL1 for substrate targeting and ubiquitin ligation."; RL Mol. Cell. Biol. 20:1382-1393(2000). RN [15] RP INDUCTION. RX PubMed=11850814; DOI=10.1038/sj.onc.1205132; RA Spiegelman V.S., Tang W., Katoh M., Slaga T.J., Fuchs S.Y.; RT "Inhibition of HOS expression and activities by Wnt pathway."; RL Oncogene 21:856-860(2002). RN [16] RP FUNCTION. RX PubMed=14603323; DOI=10.1038/nature02082; RA Busino L., Donzelli M., Chiesa M., Guardavaccaro D., Ganoth D., RA Dorrello N.V., Hershko A., Pagano M., Draetta G.F.; RT "Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA RT damage."; RL Nature 426:87-91(2003). RN [17] RP FUNCTION IN CIRCADIAN CLOCK, AND INTERACTION WITH PER3. RX PubMed=15917222; DOI=10.1074/jbc.m502862200; RA Shirogane T., Jin J., Ang X.L., Harper J.W.; RT "SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1- RT dependent degradation of the mammalian period-1 (Per1) protein."; RL J. Biol. Chem. 280:26863-26872(2005). RN [18] RP FUNCTION. RX PubMed=18575781; RA Asada S., Ikeda A., Nagao R., Hama H., Sudo T., Fukamizu A., Kasuya Y., RA Kishi T.; RT "Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFbeta-TrCP RT ubiquitin ligase."; RL Int. J. Mol. Med. 22:95-104(2008). RN [19] RP INTERACTION WITH REST. RX PubMed=18354482; DOI=10.1038/nature06641; RA Guardavaccaro D., Frescas D., Dorrello N.V., Peschiaroli A., Multani A.S., RA Cardozo T., Lasorella A., Iavarone A., Chang S., Hernando E., Pagano M.; RT "Control of chromosome stability by the beta-TrCP-REST-Mad2 axis."; RL Nature 452:365-369(2008). RN [20] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH BST2. RX PubMed=19730691; DOI=10.1371/journal.ppat.1000574; RA Mangeat B., Gers-Huber G., Lehmann M., Zufferey M., Luban J., Piguet V.; RT "HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it RT and directing its beta-TrCP2-dependent degradation."; RL PLoS Pathog. 5:E1000574-E1000574(2009). RN [21] RP FUNCTION OF THE SCF(FBXW11) COMPLEX, AND PATHWAY. RX PubMed=20347421; DOI=10.1016/j.molcel.2010.02.025; RA Wu K., Kovacev J., Pan Z.Q.; RT "Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for RT polyubiquitination on a SCF substrate."; RL Mol. Cell 37:784-796(2010). RN [22] RP FUNCTION, AND INTERACTION WITH USP47. RX PubMed=19966869; DOI=10.1038/onc.2009.430; RA Peschiaroli A., Skaar J.R., Pagano M., Melino G.; RT "The ubiquitin-specific protease USP47 is a novel beta-TRCP interactor RT regulating cell survival."; RL Oncogene 29:1384-1393(2010). RN [23] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE SCF(FBXW11) COMPLEX. RX PubMed=22017875; DOI=10.1016/j.molcel.2011.08.030; RA Gao D., Inuzuka H., Tan M.K., Fukushima H., Locasale J.W., Liu P., Wan L., RA Zhai B., Chin Y.R., Shaik S., Lyssiotis C.A., Gygi S.P., Toker A., RA Cantley L.C., Asara J.M., Harper J.W., Wei W.; RT "mTOR drives its own activation via SCF(betaTrCP)-dependent degradation of RT the mTOR inhibitor DEPTOR."; RL Mol. Cell 44:290-303(2011). RN [24] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE SCF(BTRC) COMPLEX. RX PubMed=22017876; DOI=10.1016/j.molcel.2011.08.029; RA Zhao Y., Xiong X., Sun Y.; RT "DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(betaTrCP) RT E3 ubiquitin ligase and regulates survival and autophagy."; RL Mol. Cell 44:304-316(2011). RN [25] RP FUNCTION. RX PubMed=25503564; DOI=10.1038/ncb3076; RA Pagan J.K., Marzio A., Jones M.J., Saraf A., Jallepalli P.V., Florens L., RA Washburn M.P., Pagano M.; RT "Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM RT to allow centriole separation, disengagement and licensing."; RL Nat. Cell Biol. 17:31-43(2015). RN [26] RP FUNCTION, AND INTERACTION WITH HOST FBXW11 (MICROBIAL INFECTION). RX PubMed=26837067; DOI=10.1371/journal.ppat.1005437; RA Mudhasani R., Tran J.P., Retterer C., Kota K.P., Whitehouse C.A., RA Bavari S.; RT "Protein Kinase R degradation is essential for Rift valley fever Virus RT infection and is regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 ligase."; RL PLoS Pathog. 12:E1005437-E1005437(2016). RN [27] RP FUNCTION, AND INTERACTION WITH INAVA. RX PubMed=29420262; DOI=10.1126/science.aan0814; RA Mohanan V., Nakata T., Desch A.N., Levesque C., Boroughs A., Guzman G., RA Cao Z., Creasey E., Yao J., Boucher G., Charron G., Bhan A.K., Schenone M., RA Carr S.A., Reinecker H.C., Daly M.J., Rioux J.D., Lassen K.G., Xavier R.J.; RT "C1orf106 is a colitis risk gene that regulates stability of epithelial RT adherens junctions."; RL Science 359:1161-1166(2018). RN [28] RP DEVELOPMENTAL STAGE, INVOLVEMENT IN NEDJED, AND VARIANTS NEDJED ARG-242; RP TRP-363; ASP-364; THR-365; LYS-444; GLN-447 AND LEU-447. RX PubMed=31402090; DOI=10.1016/j.ajhg.2019.07.005; RA Holt R.J., Young R.M., Crespo B., Ceroni F., Curry C.J., Bellacchio E., RA Bax D.A., Ciolfi A., Simon M., Fagerberg C.R., van Binsbergen E., RA De Luca A., Memo L., Dobyns W.B., Mohammed A.A., Clokie S.J.H., RA Zazo Seco C., Jiang Y.H., Soerensen K.P., Andersen H., Sullivan J., RA Powis Z., Chassevent A., Smith-Hicks C., Petrovski S., Antoniadi T., RA Shashi V., Gelb B.D., Wilson S.W., Gerrelli D., Tartaglia M., Chassaing N., RA Calvas P., Ragge N.K.; RT "De novo missense variants in FBXW11 cause diverse developmental phenotypes RT including brain, eye, and digit anomalies."; RL Am. J. Hum. Genet. 105:640-657(2019). RN [29] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE SCF(FBXW11) COMPLEX. RX PubMed=36608670; DOI=10.1016/j.molcel.2022.12.013; RA Nardone C., Palanski B.A., Scott D.C., Timms R.T., Barber K.W., Gu X., RA Mao A., Leng Y., Watson E.V., Schulman B.A., Cole P.A., Elledge S.J.; RT "A central role for regulated protein stability in the control of TFE3 and RT MITF by nutrients."; RL Mol. Cell 83:57-73(2023). CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box CC protein) E3 ubiquitin-protein ligase complex which mediates the CC ubiquitination and subsequent proteasomal degradation of target CC proteins (PubMed:10437795, PubMed:11158290, PubMed:10648623, CC PubMed:20347421, PubMed:19966869, PubMed:22017875, PubMed:22017876, CC PubMed:36608670). Probably recognizes and binds to phosphorylated CC target proteins: the interaction with substrates requires the CC phosphorylation of the two serine residues in the substrates' CC destruction motif D-S-G-X(2,3,4)-S (PubMed:10437795, PubMed:10648623, CC PubMed:20347421, PubMed:19966869, PubMed:22017875, PubMed:22017876, CC PubMed:36608670). SCF(FBXW11) mediates the ubiquitination of CC phosphorylated CTNNB1 and participates in Wnt signaling regulation CC (PubMed:10321728). SCF(FBXW11) plays a key role in NF-kappa-B CC activation by mediating ubiquitination of phosphorylated NFKBIA, CC leading to its degradation by the proteasome, thereby allowing the CC associated NF-kappa-B complex to translocate into the nucleus and to CC activate transcription (PubMed:10321728, PubMed:10644755, CC PubMed:10437795, PubMed:20347421). The SCF(FBXW11) complex also CC regulates NF-kappa-B by mediating ubiquitination of phosphorylated CC NFKB1: specifically ubiquitinates the p105 form of NFKB1, leading to CC its degradation (PubMed:11158290). SCF(FBXW11) mediates the CC ubiquitination of IFNAR1 (PubMed:14532120, PubMed:15337770). CC SCF(FBXW11) mediates the ubiquitination of CEP68; this is required for CC centriole separation during mitosis (PubMed:25503564). Involved in the CC oxidative stress-induced a ubiquitin-mediated decrease in RCAN1 CC (PubMed:18575781). Mediates the degradation of CDC25A induced by CC ionizing radiation in cells progressing through S phase and thus may CC function in the intra-S-phase checkpoint (PubMed:14603323). Has an CC essential role in the control of the clock-dependent transcription via CC degradation of phosphorylated PER1 and phosphorylated PER2 CC (PubMed:15917222). SCF(FBXW11) mediates the ubiquitination of CYTH1, CC and probably CYTH2 (PubMed:29420262). SCF(FBXW11) acts as a regulator CC of mTORC1 signaling pathway by catalyzing ubiquitination and subsequent CC proteasomal degradation of phosphorylated DEPTOR, TFE3 and MITF CC (PubMed:22017875, PubMed:22017876, PubMed:36608670). CC {ECO:0000269|PubMed:10321728, ECO:0000269|PubMed:10437795, CC ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:10648623, CC ECO:0000269|PubMed:11158290, ECO:0000269|PubMed:14532120, CC ECO:0000269|PubMed:14603323, ECO:0000269|PubMed:15337770, CC ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:18575781, CC ECO:0000269|PubMed:19966869, ECO:0000269|PubMed:20347421, CC ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, CC ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:29420262, CC ECO:0000269|PubMed:36608670}. CC -!- FUNCTION: (Microbial infection) Target of human immunodeficiency virus CC type 1 (HIV-1) protein VPU to polyubiquitinate and deplete BST2 from CC cells and antagonize its antiviral action. CC {ECO:0000269|PubMed:19730691}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:10321728, ECO:0000269|PubMed:10437795, CC ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:11158290, CC ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:22017875, CC ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:36608670}. CC -!- SUBUNIT: Self-associates (PubMed:10644755). Component of the CC SCF(FBXW11) complex formed of CUL1, SKP1, RBX1 and a FBXW11 dimer CC (PubMed:10066435, PubMed:10437795, PubMed:20347421, PubMed:22017875, CC PubMed:22017876, PubMed:36608670). Interacts with BST2 and USP47 CC (PubMed:19730691, PubMed:19966869). Interacts with TRIM21 CC (PubMed:16880511). Interacts with PER3 (PubMed:15917222). Interacts CC with INAVA (PubMed:29420262). Interacts with REST (PubMed:18354482). CC {ECO:0000269|PubMed:10066435, ECO:0000269|PubMed:10437795, CC ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:15917222, CC ECO:0000269|PubMed:16880511, ECO:0000269|PubMed:18354482, CC ECO:0000269|PubMed:19730691, ECO:0000269|PubMed:19966869, CC ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, CC ECO:0000269|PubMed:29420262, ECO:0000269|PubMed:36608670}. CC -!- SUBUNIT: (Microbial infection) Interact with Rift valley fever virus CC NSs (via omegaXaV motif); this interaction is important for EIF2AK2/PKR CC degradation. {ECO:0000269|PubMed:26837067}. CC -!- INTERACTION: CC Q9UKB1; Q5JTC6: AMER1; NbExp=4; IntAct=EBI-355189, EBI-6169747; CC Q9UKB1; O15169: AXIN1; NbExp=4; IntAct=EBI-355189, EBI-710484; CC Q9UKB1; P35222: CTNNB1; NbExp=4; IntAct=EBI-355189, EBI-491549; CC Q9UKB1; Q13616: CUL1; NbExp=11; IntAct=EBI-355189, EBI-359390; CC Q9UKB1; P32314: FOXN2; NbExp=4; IntAct=EBI-355189, EBI-10706164; CC Q9UKB1; P17181: IFNAR1; NbExp=8; IntAct=EBI-355189, EBI-1547250; CC Q9UKB1; Q3KP66: INAVA; NbExp=2; IntAct=EBI-355189, EBI-7545562; CC Q9UKB1; Q00987: MDM2; NbExp=4; IntAct=EBI-355189, EBI-389668; CC Q9UKB1; Q16236: NFE2L2; NbExp=2; IntAct=EBI-355189, EBI-2007911; CC Q9UKB1; P25963: NFKBIA; NbExp=2; IntAct=EBI-355189, EBI-307386; CC Q9UKB1; Q13127: REST; NbExp=3; IntAct=EBI-355189, EBI-926706; CC Q9UKB1; P63208: SKP1; NbExp=10; IntAct=EBI-355189, EBI-307486; CC Q9UKB1; P30291: WEE1; NbExp=3; IntAct=EBI-355189, EBI-914695; CC Q9UKB1; Q60793: Klf4; Xeno; NbExp=4; IntAct=EBI-355189, EBI-3043905; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q5SRY7}. Nucleus CC {ECO:0000250|UniProtKB:Q5SRY7}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=C; CC IsoId=Q9UKB1-1; Sequence=Displayed; CC Name=A; CC IsoId=Q9UKB1-2; Sequence=VSP_006765; CC Name=B; CC IsoId=Q9UKB1-3; Sequence=VSP_006766; CC -!- DEVELOPMENTAL STAGE: In the embryo, it is expressed in the developing CC eye, limbs and brain (PubMed:31402090). Expression is observed in the CC lens, retina, lips of the optic fissure closure and regions of the CC conjunctiva at Carnegie stages (CS) between CS15 and CS21. As eye CC development progresses, the stronger signal observed in the retina CC progressively shifts from the inner toward the outer retinal layers CC (PubMed:31402090). In the developing hand, expression is strong at CC CS15. At CS19 and CS21, after the digits have begun to form, strong CC expression is seen in the mesenchyme surrounding the developing CC cartilage (PubMed:31402090). In the brain, it is expressed in the CC primitive ventricles at CS17 and CS19, hypothalamus and medulla at CC CS17, and metencephalon at CS19 (PubMed:31402090). Strong expression is CC also observed in the pharyngeal arches, including the mandibular CC process and tongue at CS17 (PubMed:31402090). CC {ECO:0000269|PubMed:31402090}. CC -!- INDUCTION: Expression is negatively regulated by Wnt/beta-catenin CC pathway. {ECO:0000269|PubMed:11850814}. CC -!- DOMAIN: The N-terminal D domain mediates homodimerization. CC {ECO:0000250|UniProtKB:Q9Y297}. CC -!- DISEASE: Neurodevelopmental, jaw, eye, and digital syndrome (NEDJED) CC [MIM:618914]: An autosomal dominant syndrome characterized by variable CC features including mild-to-severe developmental delay, speech delay, CC autistic and/or stereotypical behaviors, ocular anomalies, under- or CC overdeveloped jaw, and digital anomalies such as brachydactyly, CC clinodactyly, syndactyly, and contractures. CC {ECO:0000269|PubMed:31402090}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA31671.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF176022; AAF04528.1; -; mRNA. DR EMBL; AB033279; BAA92329.1; -; mRNA. DR EMBL; AB033280; BAA92330.1; -; mRNA. DR EMBL; AB033281; BAA92331.1; -; mRNA. DR EMBL; AB014596; BAA31671.1; ALT_INIT; mRNA. DR EMBL; AK314999; BAG37495.1; -; mRNA. DR EMBL; BC026213; AAH26213.1; -; mRNA. DR CCDS; CCDS34289.1; -. [Q9UKB1-1] DR CCDS; CCDS47340.1; -. [Q9UKB1-2] DR CCDS; CCDS47341.1; -. [Q9UKB1-3] DR RefSeq; NP_036432.2; NM_012300.2. [Q9UKB1-1] DR RefSeq; NP_387448.2; NM_033644.2. [Q9UKB1-3] DR RefSeq; NP_387449.2; NM_033645.2. [Q9UKB1-2] DR PDB; 6WNX; X-ray; 2.50 A; A/D/G=114-542. DR PDBsum; 6WNX; -. DR AlphaFoldDB; Q9UKB1; -. DR SMR; Q9UKB1; -. DR BioGRID; 116887; 486. DR ComplexPortal; CPX-7821; SCF E3 ubiquitin ligase complex, FBXW11 variant. DR CORUM; Q9UKB1; -. DR DIP; DIP-27593N; -. DR ELM; Q9UKB1; -. DR IntAct; Q9UKB1; 119. DR MINT; Q9UKB1; -. DR STRING; 9606.ENSP00000265094; -. DR iPTMnet; Q9UKB1; -. DR PhosphoSitePlus; Q9UKB1; -. DR BioMuta; FBXW11; -. DR DMDM; 13124267; -. DR EPD; Q9UKB1; -. DR jPOST; Q9UKB1; -. DR MassIVE; Q9UKB1; -. DR MaxQB; Q9UKB1; -. DR PaxDb; 9606-ENSP00000265094; -. DR PeptideAtlas; Q9UKB1; -. DR ProteomicsDB; 84760; -. [Q9UKB1-1] DR ProteomicsDB; 84761; -. [Q9UKB1-2] DR ProteomicsDB; 84762; -. [Q9UKB1-3] DR Pumba; Q9UKB1; -. DR Antibodypedia; 28871; 269 antibodies from 29 providers. DR DNASU; 23291; -. DR Ensembl; ENST00000265094.9; ENSP00000265094.5; ENSG00000072803.18. [Q9UKB1-1] DR Ensembl; ENST00000296933.10; ENSP00000296933.6; ENSG00000072803.18. [Q9UKB1-3] DR Ensembl; ENST00000393802.6; ENSP00000377391.2; ENSG00000072803.18. [Q9UKB1-2] DR GeneID; 23291; -. DR KEGG; hsa:23291; -. DR UCSC; uc003mbl.2; human. [Q9UKB1-1] DR AGR; HGNC:13607; -. DR CTD; 23291; -. DR DisGeNET; 23291; -. DR GeneCards; FBXW11; -. DR HGNC; HGNC:13607; FBXW11. DR HPA; ENSG00000072803; Low tissue specificity. DR MalaCards; FBXW11; -. DR MIM; 605651; gene. DR MIM; 618914; phenotype. DR neXtProt; NX_Q9UKB1; -. DR OpenTargets; ENSG00000072803; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA28050; -. DR VEuPathDB; HostDB:ENSG00000072803; -. DR eggNOG; KOG0281; Eukaryota. DR GeneTree; ENSGT00940000155898; -. DR HOGENOM; CLU_000288_103_6_1; -. DR InParanoid; Q9UKB1; -. DR OMA; PTHTACY; -. DR OrthoDB; 337075at2759; -. DR PhylomeDB; Q9UKB1; -. DR TreeFam; TF105679; -. DR PathwayCommons; Q9UKB1; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling. DR Reactome; R-HSA-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9UKB1; -. DR SIGNOR; Q9UKB1; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 23291; 393 hits in 1211 CRISPR screens. DR ChiTaRS; FBXW11; human. DR GeneWiki; FBXW11; -. DR GenomeRNAi; 23291; -. DR Pharos; Q9UKB1; Tbio. DR PRO; PR:Q9UKB1; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9UKB1; Protein. DR Bgee; ENSG00000072803; Expressed in corpus callosum and 215 other cell types or tissues. DR ExpressionAtlas; Q9UKB1; baseline and differential. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005881; C:cytoplasmic microtubule; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0000776; C:kinetochore; IBA:GO_Central. DR GO; GO:0005875; C:microtubule associated complex; IBA:GO_Central. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central. DR GO; GO:0005635; C:nuclear envelope; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB. DR GO; GO:0070840; F:dynein complex binding; IBA:GO_Central. DR GO; GO:0051010; F:microtubule plus-end binding; IBA:GO_Central. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0048854; P:brain morphogenesis; IBA:GO_Central. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IBA:GO_Central. DR GO; GO:0007281; P:germ cell development; IBA:GO_Central. DR GO; GO:0031023; P:microtubule organizing center organization; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0007097; P:nuclear migration; IBA:GO_Central. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:UniProtKB. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0006470; P:protein dephosphorylation; ISS:UniProtKB. DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0008090; P:retrograde axonal transport; IBA:GO_Central. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0047496; P:vesicle transport along microtubule; IBA:GO_Central. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd22183; F-box_FBXW1B; 1. DR CDD; cd00200; WD40; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 6.10.250.1840; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR021977; Beta-TrCP_D. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR14604:SF6; F-BOX AND WD REPEAT DOMAIN-CONTAINING 11-B; 1. DR PANTHER; PTHR14604; WD40 REPEAT PF20; 1. DR Pfam; PF12125; Beta-TrCP_D; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF00400; WD40; 7. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM01028; Beta-TrCP_D; 1. DR SMART; SM00256; FBOX; 1. DR SMART; SM00320; WD40; 7. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50181; FBOX; 1. DR PROSITE; PS00678; WD_REPEATS_1; 5. DR PROSITE; PS50082; WD_REPEATS_2; 7. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q9UKB1; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Biological rhythms; Cell cycle; KW Cytoplasm; Disease variant; Host-virus interaction; Nucleus; KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat; KW Wnt signaling pathway. FT CHAIN 1..542 FT /note="F-box/WD repeat-containing protein 11" FT /id="PRO_0000050981" FT DOMAIN 129..167 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 238..275 FT /note="WD 1" FT REPEAT 278..315 FT /note="WD 2" FT REPEAT 318..355 FT /note="WD 3" FT REPEAT 361..398 FT /note="WD 4" FT REPEAT 401..440 FT /note="WD 5" FT REPEAT 442..478 FT /note="WD 6" FT REPEAT 490..527 FT /note="WD 7" FT REGION 67..116 FT /note="Homodimerization domain D" FT /evidence="ECO:0000250|UniProtKB:Q9Y297" FT VAR_SEQ 16..49 FT /note="Missing (in isoform A)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_006765" FT VAR_SEQ 16..48 FT /note="CSVPRSLWLGCANLVESMCALSCLQSMPSVRCL -> NTSVMEDQNEDESPK FT KNTLW (in isoform B)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_006766" FT VARIANT 242 FT /note="G -> R (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084385" FT VARIANT 363 FT /note="R -> W (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084386" FT VARIANT 364 FT /note="A -> D (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084387" FT VARIANT 365 FT /note="A -> T (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084388" FT VARIANT 444 FT /note="E -> K (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084389" FT VARIANT 447 FT /note="R -> L (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084390" FT VARIANT 447 FT /note="R -> Q (in NEDJED)" FT /evidence="ECO:0000269|PubMed:31402090" FT /id="VAR_084391" FT HELIX 119..125 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 129..136 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 141..148 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 152..160 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 163..174 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 176..184 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 188..190 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 202..225 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 229..234 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 243..248 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 250..257 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 262..266 FT /evidence="ECO:0007829|PDB:6WNX" FT TURN 267..269 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 272..276 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 283..288 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 290..297 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 300..306 FT /evidence="ECO:0007829|PDB:6WNX" FT TURN 307..309 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 312..317 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 323..329 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 332..337 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 340..351 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 353..360 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 366..371 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 373..380 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 385..389 FT /evidence="ECO:0007829|PDB:6WNX" FT TURN 390..392 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 395..399 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 406..412 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 415..420 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 425..429 FT /evidence="ECO:0007829|PDB:6WNX" FT TURN 430..432 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 435..439 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 446..451 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 453..460 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 463..469 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 470..474 FT /evidence="ECO:0007829|PDB:6WNX" FT HELIX 480..482 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 484..489 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 495..501 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 504..509 FT /evidence="ECO:0007829|PDB:6WNX" FT STRAND 512..521 FT /evidence="ECO:0007829|PDB:6WNX" SQ SEQUENCE 542 AA; 62091 MW; 7CD40087EFAA5C8A CRC64; MEPDSVIEDK TIELMCSVPR SLWLGCANLV ESMCALSCLQ SMPSVRCLQI SNGTSSVIVS RKRPSEGNYQ KEKDLCIKYF DQWSESDQVE FVEHLISRMC HYQHGHINSY LKPMLQRDFI TALPEQGLDH IAENILSYLD ARSLCAAELV CKEWQRVISE GMLWKKLIER MVRTDPLWKG LSERRGWDQY LFKNRPTDGP PNSFYRSLYP KIIQDIETIE SNWRCGRHNL QRIQCRSENS KGVYCLQYDD EKIISGLRDN SIKIWDKTSL ECLKVLTGHT GSVLCLQYDE RVIVTGSSDS TVRVWDVNTG EVLNTLIHHN EAVLHLRFSN GLMVTCSKDR SIAVWDMASA TDITLRRVLV GHRAAVNVVD FDDKYIVSAS GDRTIKVWST STCEFVRTLN GHKRGIACLQ YRDRLVVSGS SDNTIRLWDI ECGACLRVLE GHEELVRCIR FDNKRIVSGA YDGKIKVWDL QAALDPRAPA STLCLRTLVE HSGRVFRLQF DEFQIISSSH DDTILIWDFL NVPPSAQNET RSPSRTYTYI SR //