ID FBW1A_HUMAN Reviewed; 605 AA. AC Q9Y297; B5MD49; Q5W141; Q5W142; Q9Y213; DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 229. DE RecName: Full=F-box/WD repeat-containing protein 1A; DE AltName: Full=E3RSIkappaB; DE AltName: Full=Epididymis tissue protein Li 2a; DE AltName: Full=F-box and WD repeats protein beta-TrCP; DE AltName: Full=pIkappaBalpha-E3 receptor subunit {ECO:0000303|PubMed:9859996}; GN Name=BTRC; Synonyms=BTRCP, FBW1A, FBXW1A; 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] (ISOFORM 1), FUNCTION, AND PATHWAY. RX PubMed=9859996; DOI=10.1038/25159; RA Yaron A., Hatzubai A., Davis M., Lavon I., Amit S., Manning A.M., RA Andersen J.S., Mann M., Mercurio F., Ben-Neriah Y.; RT "Identification of the receptor component of the IkappaBalpha-ubiquitin RT ligase."; RL Nature 396:590-594(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH HIV-1 VPU. RC TISSUE=Lymphoid tissue; RX PubMed=9660940; DOI=10.1016/s1097-2765(00)80056-8; RA Margottin F., Bour S.P., Durand H., Selig L., Benichou S., Richard V., RA Thomas D., Strebel K., Benarous R.; RT "A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu RT connects CD4 to the ER degradation pathway through an F-box motif."; RL Mol. Cell 1:565-574(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Epididymis; RX PubMed=20736409; DOI=10.1074/mcp.m110.001719; RA Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C., RA Jin S., Liu J., Zhu P., Liu Y.; RT "Systematic mapping and functional analysis of a family of human epididymal RT secretory sperm-located proteins."; RL Mol. Cell. Proteomics 9:2517-2528(2010). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [9] RP IDENTIFICATION IN THE SCF(BTRC) COMPLEX, AND FUNCTION IN UBIQUITINATION OF RP NFKBIA. 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 [10] RP INTERACTION WITH NFKBIB AND NFKBIE, AND FUNCTION IN UBIQUITINATION OF RP NFKBIB AND NFKBIE. RX PubMed=10497169; DOI=10.1074/jbc.274.40.28169; RA Shirane M., Hatakeyama S., Hattori K., Nakayama K., Nakayama K.; RT "Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and RT IkappaBepsilon mediated by the F-box protein FWD1."; RL J. Biol. Chem. 274:28169-28174(1999). RN [11] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE SCF(BTRC) COMPLEX. RX PubMed=9990852; DOI=10.1101/gad.13.3.270; RA Winston J.T., Strack P., Beer-Romero P., Chu C.Y., Elledge S.J., RA Harper J.W.; RT "The SCF(beta-TRCP)-ubiquitin ligase complex associates specifically with RT phosphorylated destruction motifs in I-kappa-B-alpha and beta-catenin and RT stimulates I-kappa-B-alpha ubiquitination in vitro."; RL Genes Dev. 13:270-283(1999). RN [12] RP INTERACTION WITH NFKB1, FUNCTION IN UBIQUITINATION OF NFKB1, AND PATHWAY. RX PubMed=10835356; DOI=10.1093/emboj/19.11.2580; RA Orian A., Gonen H., Bercovich B., Fajerman I., Eytan E., Israel A., RA Mercurio F., Iwai K., Schwartz A.L., Ciechanover A.; RT "SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 RT requires phosphorylation of its C-terminus by IkappaB kinase."; RL EMBO J. 19:2580-2591(2000). RN [13] RP SELF-ASSOCIATION, INTERACTION WITH FBXW11 AND NFKBIA, AND FUNCTION IN RP UBIQUITINATION OF NFKBIA. 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 [14] RP INTERACTION WITH UBQLN1. RC TISSUE=B-cell; RX PubMed=10983987; DOI=10.1016/s1097-2765(00)00040-x; RA Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E., Kedersha N.L., RA Gill G., Howley P.M.; RT "The hPLIC proteins may provide a link between the ubiquitination machinery RT and the proteasome."; RL Mol. Cell 6:409-419(2000). RN [15] RP INTERACTION WITH PHOSPHORYLATED SMAD3, AND FUNCTION IN SMAD3 RP UBIQUITINATION. RX PubMed=11359933; DOI=10.1091/mbc.12.5.1431; RA Fukuchi M., Imamura T., Chiba T., Ebisawa T., Kawabata M., Tanaka K., RA Miyazono K.; RT "Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of RT ROC1 and associated proteins."; RL Mol. Biol. Cell 12:1431-1443(2001). RN [16] RP INTERACTION WITH PHOSPHORYLATED ATF4, AND FUNCTION IN ATF4 UBIQUITINATION. RX PubMed=11238952; DOI=10.1128/mcb.21.6.2192-2202.2001; RA Lassot I., Segeral E., Berlioz-Torrent C., Durand H., Groussin L., Hai T., RA Benarous R., Margottin-Goguet F.; RT "ATF4 degradation relies on a phosphorylation-dependent interaction with RT the SCF(betaTrCP) ubiquitin ligase."; RL Mol. Cell. Biol. 21:2192-2202(2001). RN [17] 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 [18] RP FUNCTION IN NFKB2 UBIQUITINATION. RX PubMed=11994270; DOI=10.1074/jbc.c200151200; RA Fong A., Sun S.C.; RT "Genetic evidence for the essential role of beta-transducin repeat- RT containing protein in the inducible processing of NF-kappa B2/p100."; RL J. Biol. Chem. 277:22111-22114(2002). RN [19] RP INTERACTION WITH PHOSPHORYLATED CTNNB1. RX PubMed=12077367; DOI=10.1242/jcs.115.13.2771; RA Sadot E., Conacci-Sorrell M., Zhurinsky J., Shnizer D., Lando Z., RA Zharhary D., Kam Z., Ben-Ze'ev A., Geiger B.; RT "Regulation of S33/S37 phosphorylated beta-catenin in normal and RT transformed cells."; RL J. Cell Sci. 115:2771-2780(2002). RN [20] RP INTERACTION WITH CDC34 AND UBE2R2. RX PubMed=12037680; DOI=10.1038/sj.onc.1205574; RA Semplici F., Meggio F., Pinna L.A., Oliviero S.; RT "CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B RT induces its interaction with beta-TrCP and enhances beta-catenin RT degradation."; RL Oncogene 21:3978-3987(2002). RN [21] RP INTERACTION WITH PHOSPHORYLATED FBXO5, AND FUNCTION IN FBXO5 RP UBIQUITINATION. RX PubMed=12791267; DOI=10.1016/s1534-5807(03)00153-9; RA Margottin-Goguet F., Hsu J.Y., Loktev A., Hsieh H.-M., Reimann J.D.R., RA Jackson P.K.; RT "Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase RT activates the anaphase promoting complex to allow progression beyond RT prometaphase."; RL Dev. Cell 4:813-826(2003). RN [22] RP INTERACTION WITH PHOSPHORYLATED CDC25A, AND FUNCTION IN CDC25A RP UBIQUITINATION. RX PubMed=14681206; DOI=10.1101/gad.1157503; RA Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W.; RT "SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein RT phosphatase."; RL Genes Dev. 17:3062-3074(2003). RN [23] RP INTERACTION WITH PHOSPHORYLATED DLG1, AND FUNCTION IN DLG1 UBIQUITINATION. RX PubMed=12902344; DOI=10.1074/jbc.m302799200; RA Mantovani F., Banks L.; RT "Regulation of the discs large tumor suppressor by a phosphorylation- RT dependent interaction with the beta-TrCP ubiquitin ligase receptor."; RL J. Biol. Chem. 278:42477-42486(2003). RN [24] RP INTERACTION WITH PHOSPHORYLATED CDC25A, AND FUNCTION IN CDC25A RP UBIQUITINATION. 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 [25] RP INTERACTION WITH PHOSPHORYLATED SMAD4, AND FUNCTION IN SMAD4 RP UBIQUITINATION. RX PubMed=14988407; DOI=10.1074/jbc.c400005200; RA Wan M., Tang Y., Tytler E.M., Lu C., Jin B., Vickers S.M., Yang L., Shi X., RA Cao X.; RT "Smad4 protein stability is regulated by ubiquitin ligase SCF beta-TrCP1."; RL J. Biol. Chem. 279:14484-14487(2004). RN [26] RP FUNCTION. RX PubMed=14673179; DOI=10.1128/mcb.24.1.475-486.2004; RA Cohen S., Achbert-Weiner H., Ciechanover A.; RT "Dual effects of IkappaB kinase beta-mediated phosphorylation on p105 fate: RT SCF(beta-TrCP)-dependent degradation and SCF(beta-TrCP)-independent RT processing."; RL Mol. Cell. Biol. 24:475-486(2004). RN [27] RP FUNCTION, AND INTERACTION WITH SNAI1. RX PubMed=15448698; DOI=10.1038/ncb1173; RA Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C.; RT "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control RT of epithelial-mesenchymal transition."; RL Nat. Cell Biol. 6:931-940(2004). RN [28] RP INTERACTION WITH SNAI1. RX PubMed=15647282; DOI=10.1074/jbc.m413878200; RA Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J.; RT "Wnt-dependent regulation of the E-cadherin repressor snail."; RL J. Biol. Chem. 280:11740-11748(2005). RN [29] RP FUNCTION IN CIRCADIAN CLOCK, AND INTERACTION WITH PER1 AND 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 [30] RP INTERACTION WITH CUL4A AND DDB1. RX PubMed=17079684; DOI=10.1101/gad.1483206; RA He Y.J., McCall C.M., Hu J., Zeng Y., Xiong Y.; RT "DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 RT ubiquitin ligases."; RL Genes Dev. 20:2949-2954(2006). RN [31] RP INTERACTION WITH GLI3. RX PubMed=16705181; DOI=10.1128/mcb.02183-05; RA Tempe D., Casas M., Karaz S., Blanchet-Tournier M.F., Concordet J.P.; RT "Multisite protein kinase A and glycogen synthase kinase 3beta RT phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP."; RL Mol. Cell. Biol. 26:4316-4326(2006). RN [32] RP FUNCTION. RX PubMed=16371461; DOI=10.1073/pnas.0509927103; RA Wang B., Li Y.; RT "Evidence for the direct involvement of {beta}TrCP in Gli3 protein RT processing."; RL Proc. Natl. Acad. Sci. U.S.A. 103:33-38(2006). RN [33] RP INTERACTION WITH HSF1. RX PubMed=18794143; DOI=10.1158/0008-5472.can-08-0129; RA Lee Y.J., Kim E.H., Lee J.S., Jeoung D., Bae S., Kwon S.H., Lee Y.S.; RT "HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential RT for mitotic progression."; RL Cancer Res. 68:7550-7560(2008). RN [34] RP FUNCTION, AND 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 [35] RP INTERACTION WITH CLU. RX PubMed=20068069; DOI=10.1158/1541-7786.mcr-09-0277; RA Zoubeidi A., Ettinger S., Beraldi E., Hadaschik B., Zardan A., Klomp L.W., RA Nelson C.C., Rennie P.S., Gleave M.E.; RT "Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB RT activity in prostate cancer cells."; RL Mol. Cancer Res. 8:119-130(2010). RN [36] RP FUNCTION, PATHWAY, IDENTIFICATION IN THE SCF(BTRC) COMPLEX, AND MUTAGENESIS RP OF ARG-510. 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 [37] 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 [38] RP FUNCTION, PATHWAY, AND IDENTIFICATION IN THE SCF(BTRC) COMPLEX. RX PubMed=22017877; DOI=10.1016/j.molcel.2011.09.005; RA Duan S., Skaar J.R., Kuchay S., Toschi A., Kanarek N., Ben-Neriah Y., RA Pagano M.; RT "mTOR generates an auto-amplification loop by triggering the betaTrCP- and RT CK1alpha-dependent degradation of DEPTOR."; RL Mol. Cell 44:317-324(2011). RN [39] RP FUNCTION. RX PubMed=21258371; DOI=10.1038/ncb2153; RA Huang Z., Wu Q., Guryanova O.A., Cheng L., Shou W., Rich J.N., Bao S.; RT "Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural RT progenitor cells."; RL Nat. Cell Biol. 13:142-152(2011). RN [40] RP INTERACTION WITH IL10RA, AND FUNCTION. RX PubMed=22087322; DOI=10.1371/journal.pone.0027464; RA Jiang H., Lu Y., Yuan L., Liu J.; RT "Regulation of interleukin-10 receptor ubiquitination and stability by RT beta-TrCP-containing ubiquitin E3 ligase."; RL PLoS ONE 6:E27464-E27464(2011). RN [41] RP INTERACTION WITH VACCINIA VIRUS PROTEIN A49 (MICROBIAL INFECTION). RX PubMed=23468625; DOI=10.1371/journal.ppat.1003183; RA Mansur D.S., Maluquer de Motes C., Unterholzner L., Sumner R.P., RA Ferguson B.J., Ren H., Strnadova P., Bowie A.G., Smith G.L.; RT "Poxvirus targeting of E3 ligase beta-TrCP by molecular mimicry: a RT mechanism to inhibit NF-kappaB activation and promote immune evasion and RT virulence."; RL PLoS Pathog. 9:E1003183-E1003183(2013). RN [42] RP FUNCTION, AND INTERACTION WITH CEP68. RX PubMed=25704143; DOI=10.1016/j.ejcb.2015.01.004; RA Man X., Megraw T.L., Lim Y.P.; RT "Cep68 can be regulated by Nek2 and SCF complex."; RL Eur. J. Cell Biol. 94:162-172(2015). RN [43] RP FUNCTION, AND INTERACTION WITH CEP68. 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 [44] RP 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 [45] RP FUNCTION, UBIQUITINATION, AND DEUBIQUITINATION. RX PubMed=33110214; DOI=10.1038/s41418-020-00649-z; RA Cho J.H., Kim K., Kim S.A., Park S., Park B.O., Kim J.H., Kim S.Y., RA Kwon M.J., Han M.H., Lee S.B., Park B.C., Park S.G., Kim J.H., Kim S.; RT "Deubiquitinase OTUD5 is a positive regulator of mTORC1 and mTORC2 RT signaling pathways."; RL Cell Death Differ. 28:900-914(2021). RN [46] RP FUNCTION, PATHWAY, IDENTIFICATION IN THE SCF(BTRC) COMPLEX, AND MUTAGENESIS RP OF TYR-307; ARG-321 AND ARG-510. 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). RN [47] RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 175-605 IN COMPLEX WITH SKP1 AND RP CTNNB1. RX PubMed=12820959; DOI=10.1016/s1097-2765(03)00234-x; RA Wu G., Xu G., Schulman B.A., Jeffrey P.D., Harper J.W., Pavletich N.P.; RT "Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif RT binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase."; RL Mol. Cell 11:1445-1456(2003). RN [48] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 128-177, DOMAIN, AND SUBUNIT. RX PubMed=17574027; DOI=10.1016/j.cell.2007.04.042; RA Tang X., Orlicky S., Lin Z., Willems A., Neculai D., Ceccarelli D., RA Mercurio F., Shilton B.H., Sicheri F., Tyers M.; RT "Suprafacial orientation of the SCFCdc4 dimer accommodates multiple RT geometries for substrate ubiquitination."; RL Cell 129:1165-1176(2007). 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:10066435, PubMed:10497169, PubMed:9990852, CC PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, CC PubMed:11158290, PubMed:11994270, PubMed:12791267, PubMed:12902344, CC PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, CC PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, CC PubMed:9859996, PubMed:22017875, PubMed:22017876, PubMed:22017877, CC PubMed:22087322, PubMed:36608670). Recognizes and binds to CC phosphorylated target proteins (PubMed:10066435, PubMed:10497169, CC PubMed:9990852, PubMed:10644755, PubMed:10835356, PubMed:11238952, CC PubMed:11359933, PubMed:11158290, PubMed:11994270, PubMed:12791267, CC PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, CC PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, CC PubMed:25704143, PubMed:9859996, PubMed:22017875, PubMed:22017876, CC PubMed:22017877, PubMed:22087322, PubMed:36608670). SCF(BTRC) mediates CC the ubiquitination of CTNNB1 and participates in Wnt signaling CC (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the CC ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, CC PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, CC PubMed:11238952, PubMed:14681206, PubMed:14603323). SCF(BTRC) mediates CC the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees CC the associated NFKB1 to translocate into the nucleus and to activate CC transcription (PubMed:9859996, PubMed:10066435, PubMed:10497169, CC PubMed:10644755). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys- CC 22' (PubMed:10066435). The SCF(FBXW11) complex also regulates NF-kappa- CC B by mediating ubiquitination of phosphorylated NFKB1: specifically CC ubiquitinates the p105 form of NFKB1, leading to its degradation CC (PubMed:10835356, PubMed:11158290, PubMed:14673179). SCF(BTRC) mediates CC the ubiquitination of CEP68; this is required for centriole separation CC during mitosis (PubMed:25704143, PubMed:25503564). SCF(BTRC) mediates CC the ubiquitination and subsequent degradation of nuclear NFE2L1 (By CC similarity). Has an essential role in the control of the clock- CC dependent transcription via degradation of phosphorylated PER1 and PER2 CC (PubMed:15917222). May be involved in ubiquitination and subsequent CC proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein CC ligase. Required for activation of NFKB-mediated transcription by IL1B, CC MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of CC GLI3 (PubMed:16371461). Mediates ubiquitination of REST, thereby CC leading to its proteasomal degradation (PubMed:21258371, CC PubMed:18354482). SCF(BTRC) mediates the ubiquitination and subsequent CC proteasomal degradation of KLF4; thereby negatively regulating cell CC pluripotency maintenance and embryogenesis (By similarity). SCF(BTRC) CC acts as a regulator of mTORC1 signaling pathway by catalyzing CC ubiquitination and subsequent proteasomal degradation of phosphorylated CC DEPTOR, TFE3 and MITF (PubMed:22017875, PubMed:22017876, CC PubMed:22017877, PubMed:33110214, PubMed:36608670). CC {ECO:0000250|UniProtKB:Q3ULA2, ECO:0000269|PubMed:10066435, CC ECO:0000269|PubMed:10497169, ECO:0000269|PubMed:10644755, CC ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11158290, CC ECO:0000269|PubMed:11238952, ECO:0000269|PubMed:11359933, CC ECO:0000269|PubMed:11994270, ECO:0000269|PubMed:12077367, CC ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:12820959, CC ECO:0000269|PubMed:12902344, ECO:0000269|PubMed:14603323, CC ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:14681206, CC ECO:0000269|PubMed:14988407, ECO:0000269|PubMed:15448698, CC ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16371461, CC ECO:0000269|PubMed:18354482, ECO:0000269|PubMed:21258371, CC ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, CC ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:22087322, CC ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, CC ECO:0000269|PubMed:33110214, ECO:0000269|PubMed:9859996, CC ECO:0000269|PubMed:9990852}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11158290, CC ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, CC ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:36608670, CC ECO:0000269|PubMed:9859996, ECO:0000269|PubMed:9990852}. CC -!- SUBUNIT: Homodimer. Self-associates. Component of the SCF(BTRC) complex CC formed of CUL1, SKP1, RBX1 and a BTRC dimer (PubMed:10066435, CC PubMed:9990852, PubMed:22017875, PubMed:22017876, PubMed:22017877, CC PubMed:36608670). Direct interaction with SKP1 occurs via the F-box CC domain. Interacts with phosphorylated ubiquitination substrates SMAD3 CC and SMAD4. Interacts with phosphorylated ubiquitination substrates CC CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 CC subunit, ATF4, CDC25A, DLG1, FBXO5 and SNAI1; the interaction requires CC the phosphorylation of the 2 serine residues in the substrate CC destruction motif D-S-G-X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 CC and UBE2R2. Interacts with FBXW11. Interacts with CUL4A and DDB1. Part CC of a SCF(BTRC)-like complex lacking CUL1, which is associated with CC phosphorylated NKBIA and RELA; RELA interacts directly with NFKBIA. CC Interacts with the phosphorylated form of GLI3. Interacts with CLU. CC Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. CC Interacts with phosphorylated ubiquitination substrate CEP68 CC (PubMed:25704143, PubMed:25503564). Interacts with ZC3H12A; this CC interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB- CC dependent manner (By similarity). Interacts with HSF1; this interaction CC occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, CC a process inhibited by CDC20 (PubMed:18794143). Interacts with NFE2L1 CC (By similarity). Interacts with INAVA (PubMed:29420262). Interacts with CC IL10RA; this interaction leads to IL10RA ubiquitination and subsequent CC degradation (PubMed:22087322). Interacts with REST (PubMed:18354482). CC Interacts with KLF4; this interaction leads to KLF4 ubiquitination and CC subsequent degradation (By similarity). {ECO:0000250|UniProtKB:Q3ULA2, CC ECO:0000269|PubMed:10066435, ECO:0000269|PubMed:10497169, CC ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:10835356, CC ECO:0000269|PubMed:10983987, ECO:0000269|PubMed:11238952, CC ECO:0000269|PubMed:11359933, ECO:0000269|PubMed:12037680, CC ECO:0000269|PubMed:12077367, ECO:0000269|PubMed:12791267, CC ECO:0000269|PubMed:12820959, ECO:0000269|PubMed:12902344, CC ECO:0000269|PubMed:14603323, ECO:0000269|PubMed:14681206, CC ECO:0000269|PubMed:14988407, ECO:0000269|PubMed:15448698, CC ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:15917222, CC ECO:0000269|PubMed:16705181, ECO:0000269|PubMed:17079684, CC ECO:0000269|PubMed:17574027, ECO:0000269|PubMed:18354482, CC ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:20068069, CC ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, CC ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:22087322, CC ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, CC ECO:0000269|PubMed:29420262, ECO:0000269|PubMed:36608670, CC ECO:0000269|PubMed:9990852}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus A49; this CC interaction inhibits NF-kappa-B activation. CC {ECO:0000269|PubMed:23468625}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Vpu. CC {ECO:0000269|PubMed:9660940}. CC -!- INTERACTION: CC Q9Y297; Q5JTC6: AMER1; NbExp=5; IntAct=EBI-307461, EBI-6169747; CC Q9Y297; P18848: ATF4; NbExp=21; IntAct=EBI-307461, EBI-492498; CC Q9Y297; Q9Y2T1: AXIN2; NbExp=3; IntAct=EBI-307461, EBI-4400025; CC Q9Y297; Q76N32: CEP68; NbExp=2; IntAct=EBI-307461, EBI-9051024; CC Q9Y297; Q7L5N1: COPS6; NbExp=2; IntAct=EBI-307461, EBI-486838; CC Q9Y297; P35222: CTNNB1; NbExp=8; IntAct=EBI-307461, EBI-491549; CC Q9Y297; Q13616: CUL1; NbExp=11; IntAct=EBI-307461, EBI-359390; CC Q9Y297; Q12959: DLG1; NbExp=2; IntAct=EBI-307461, EBI-357481; CC Q9Y297; P10070: GLI2; NbExp=4; IntAct=EBI-307461, EBI-10821567; CC Q9Y297; P28799: GRN; NbExp=3; IntAct=EBI-307461, EBI-747754; CC Q9Y297; Q13651: IL10RA; NbExp=6; IntAct=EBI-307461, EBI-1031656; CC Q9Y297; Q3KP66: INAVA; NbExp=2; IntAct=EBI-307461, EBI-7545562; CC Q9Y297; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-307461, EBI-1055254; CC Q9Y297; Q02750: MAP2K1; NbExp=3; IntAct=EBI-307461, EBI-492564; CC Q9Y297; Q00987: MDM2; NbExp=9; IntAct=EBI-307461, EBI-389668; CC Q9Y297; P49821: NDUFV1; NbExp=3; IntAct=EBI-307461, EBI-748312; CC Q9Y297; Q15843: NEDD8; NbExp=2; IntAct=EBI-307461, EBI-716247; CC Q9Y297; Q16621: NFE2; NbExp=3; IntAct=EBI-307461, EBI-726369; CC Q9Y297; Q16236: NFE2L2; NbExp=2; IntAct=EBI-307461, EBI-2007911; CC Q9Y297; Q5HYW2: NHSL2; NbExp=3; IntAct=EBI-307461, EBI-2859639; CC Q9Y297; O00444: PLK4; NbExp=4; IntAct=EBI-307461, EBI-746202; CC Q9Y297; Q99952: PTPN18; NbExp=2; IntAct=EBI-307461, EBI-1384210; CC Q9Y297; Q99952-1: PTPN18; NbExp=2; IntAct=EBI-307461, EBI-12739708; CC Q9Y297; Q8WWW0: RASSF5; NbExp=4; IntAct=EBI-307461, EBI-367390; CC Q9Y297; Q8WWW0-2: RASSF5; NbExp=3; IntAct=EBI-307461, EBI-960502; CC Q9Y297; Q13127: REST; NbExp=10; IntAct=EBI-307461, EBI-926706; CC Q9Y297; P63208: SKP1; NbExp=17; IntAct=EBI-307461, EBI-307486; CC Q9Y297; Q13485: SMAD4; NbExp=2; IntAct=EBI-307461, EBI-347263; CC Q9Y297; O95863: SNAI1; NbExp=2; IntAct=EBI-307461, EBI-1045459; CC Q9Y297; O75410: TACC1; NbExp=4; IntAct=EBI-307461, EBI-624237; CC Q9Y297; O75410-7: TACC1; NbExp=6; IntAct=EBI-307461, EBI-12007872; CC Q9Y297; P04637: TP53; NbExp=2; IntAct=EBI-307461, EBI-366083; CC Q9Y297; Q9NQ86: TRIM36; NbExp=3; IntAct=EBI-307461, EBI-2341518; CC Q9Y297; Q9C026: TRIM9; NbExp=7; IntAct=EBI-307461, EBI-720828; CC Q9Y297; Q9C026-5: TRIM9; NbExp=4; IntAct=EBI-307461, EBI-16437499; CC Q9Y297; P30291: WEE1; NbExp=2; IntAct=EBI-307461, EBI-914695; CC Q9Y297; O76024: WFS1; NbExp=3; IntAct=EBI-307461, EBI-720609; CC Q9Y297; Q5D1E8: ZC3H12A; NbExp=3; IntAct=EBI-307461, EBI-747793; CC Q9Y297; Q62696: Dlg1; Xeno; NbExp=3; IntAct=EBI-307461, EBI-389325; CC Q9Y297; Q60793: Klf4; Xeno; NbExp=3; IntAct=EBI-307461, EBI-3043905; CC Q9Y297-2; P18848: ATF4; NbExp=5; IntAct=EBI-8826333, EBI-492498; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q3ULA2}. Nucleus CC {ECO:0000250|UniProtKB:Q3ULA2}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y297-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y297-2; Sequence=VSP_006764; CC -!- TISSUE SPECIFICITY: Expressed in epididymis (at protein level). CC {ECO:0000269|PubMed:20736409}. CC -!- DOMAIN: The N-terminal D domain mediates homodimerization. CC {ECO:0000269|PubMed:17574027}. CC -!- PTM: Ubiquitinated (PubMed:33110214). Deubiquitinated by OTUD5, CC promoting its stability (PubMed:33110214). CC {ECO:0000269|PubMed:33110214}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/451/BTRC"; 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; AF101784; AAD08702.1; -; mRNA. DR EMBL; Y14153; CAA74572.1; -; mRNA. DR EMBL; AF129530; AAF04464.1; -; mRNA. DR EMBL; GU727631; ADU87633.1; -; mRNA. DR EMBL; AK313353; BAG36155.1; -; mRNA. DR EMBL; AL133387; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445463; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL627424; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49772.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49774.1; -; Genomic_DNA. DR EMBL; BC027994; AAH27994.1; -; mRNA. DR CCDS; CCDS7511.1; -. [Q9Y297-2] DR CCDS; CCDS7512.1; -. [Q9Y297-1] DR RefSeq; NP_003930.1; NM_003939.4. [Q9Y297-2] DR RefSeq; NP_378663.1; NM_033637.3. [Q9Y297-1] DR PDB; 1P22; X-ray; 2.95 A; A=175-605. DR PDB; 2P64; X-ray; 2.50 A; A/B=128-177. DR PDB; 6M90; X-ray; 2.05 A; A=175-605. DR PDB; 6M91; X-ray; 2.40 A; A=175-605. DR PDB; 6M92; X-ray; 2.35 A; A=175-605. DR PDB; 6M93; X-ray; 2.50 A; A=175-605. DR PDB; 6M94; X-ray; 2.70 A; A=175-605. DR PDB; 6TTU; EM; 3.70 A; T=1-605. DR PDBsum; 1P22; -. DR PDBsum; 2P64; -. DR PDBsum; 6M90; -. DR PDBsum; 6M91; -. DR PDBsum; 6M92; -. DR PDBsum; 6M93; -. DR PDBsum; 6M94; -. DR PDBsum; 6TTU; -. DR AlphaFoldDB; Q9Y297; -. DR EMDB; EMD-10585; -. DR SMR; Q9Y297; -. DR BioGRID; 114457; 761. DR ComplexPortal; CPX-2365; SCF E3 ubiquitin ligase complex, BTRC variant. DR CORUM; Q9Y297; -. DR DIP; DIP-31607N; -. DR IntAct; Q9Y297; 156. DR MINT; Q9Y297; -. DR STRING; 9606.ENSP00000359206; -. DR GlyGen; Q9Y297; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y297; -. DR PhosphoSitePlus; Q9Y297; -. DR BioMuta; BTRC; -. DR DMDM; 13124271; -. DR EPD; Q9Y297; -. DR jPOST; Q9Y297; -. DR MassIVE; Q9Y297; -. DR MaxQB; Q9Y297; -. DR PaxDb; 9606-ENSP00000359206; -. DR PeptideAtlas; Q9Y297; -. DR ProteomicsDB; 85705; -. [Q9Y297-1] DR ProteomicsDB; 85706; -. [Q9Y297-2] DR Pumba; Q9Y297; -. DR Antibodypedia; 31277; 421 antibodies from 32 providers. DR DNASU; 8945; -. DR Ensembl; ENST00000370187.8; ENSP00000359206.3; ENSG00000166167.18. [Q9Y297-1] DR Ensembl; ENST00000408038.6; ENSP00000385339.2; ENSG00000166167.18. [Q9Y297-2] DR GeneID; 8945; -. DR KEGG; hsa:8945; -. DR MANE-Select; ENST00000370187.8; ENSP00000359206.3; NM_033637.4; NP_378663.1. DR UCSC; uc001kta.5; human. [Q9Y297-1] DR AGR; HGNC:1144; -. DR CTD; 8945; -. DR DisGeNET; 8945; -. DR GeneCards; BTRC; -. DR HGNC; HGNC:1144; BTRC. DR HPA; ENSG00000166167; Low tissue specificity. DR MalaCards; BTRC; -. DR MIM; 603482; gene. DR neXtProt; NX_Q9Y297; -. DR OpenTargets; ENSG00000166167; -. DR Orphanet; 2440; Isolated split hand-split foot malformation. DR PharmGKB; PA25465; -. DR VEuPathDB; HostDB:ENSG00000166167; -. DR eggNOG; KOG0281; Eukaryota. DR GeneTree; ENSGT00940000159672; -. DR HOGENOM; CLU_000288_103_6_1; -. DR InParanoid; Q9Y297; -. DR OMA; GIAHVWS; -. DR OrthoDB; 337075at2759; -. DR PhylomeDB; Q9Y297; -. DR TreeFam; TF105679; -. DR PathwayCommons; Q9Y297; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-174113; SCF-beta-TrCP mediated degradation of Emi1. DR Reactome; R-HSA-180534; Vpu mediated degradation of CD4. DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex. 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-3769402; Deactivation of the beta-catenin transactivating complex. DR Reactome; R-HSA-400253; Circadian Clock. 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-5610780; Degradation of GLI1 by the proteasome. DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome. DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome. 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-9020702; Interleukin-1 signaling. DR Reactome; R-HSA-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9Y297; -. DR SIGNOR; Q9Y297; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 8945; 20 hits in 1208 CRISPR screens. DR ChiTaRS; BTRC; human. DR EvolutionaryTrace; Q9Y297; -. DR GeneWiki; BTRC_(gene); -. DR GenomeRNAi; 8945; -. DR Pharos; Q9Y297; Tbio. DR PRO; PR:Q9Y297; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9Y297; Protein. DR Bgee; ENSG00000166167; Expressed in secondary oocyte and 179 other cell types or tissues. DR ExpressionAtlas; Q9Y297; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IC:UniProt. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0008013; F:beta-catenin binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro. DR GO; GO:0045309; F:protein phosphorylated amino acid binding; IEA:Ensembl. DR GO; GO:1990757; F:ubiquitin ligase activator activity; IDA:ParkinsonsUK-UCL. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; TAS:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; TAS:BHF-UCL. DR GO; GO:0038061; P:non-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:1904668; P:positive regulation of ubiquitin protein ligase activity; IDA:ParkinsonsUK-UCL. 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:0070936; P:protein K48-linked ubiquitination; IEA:Ensembl. DR GO; GO:0000209; P:protein polyubiquitination; IDA:ParkinsonsUK-UCL. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IC:ParkinsonsUK-UCL. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0042752; P:regulation of circadian rhythm; IDA:UniProtKB. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IEA:Ensembl. 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:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR CDD; cd22182; F-box_FBXW1A; 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 IDEAL; IID00254; -. 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:SF5; F-BOX_WD REPEAT-CONTAINING PROTEIN 1A; 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; 6. DR PROSITE; PS50082; WD_REPEATS_2; 7. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q9Y297; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Biological rhythms; Cytoplasm; KW Host-virus interaction; Ligase; Nucleus; Reference proteome; Repeat; KW Ubl conjugation; Ubl conjugation pathway; WD repeat; Wnt signaling pathway. FT CHAIN 1..605 FT /note="F-box/WD repeat-containing protein 1A" FT /id="PRO_0000050980" FT DOMAIN 190..228 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 301..338 FT /note="WD 1" FT REPEAT 341..378 FT /note="WD 2" FT REPEAT 381..418 FT /note="WD 3" FT REPEAT 424..461 FT /note="WD 4" FT REPEAT 464..503 FT /note="WD 5" FT REPEAT 505..541 FT /note="WD 6" FT REPEAT 553..590 FT /note="WD 7" FT REGION 128..177 FT /note="Homodimerization domain D" FT REGION 190..228 FT /note="Required for down-regulation of SNAI1" FT VAR_SEQ 17..52 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10531035, FT ECO:0000303|PubMed:9660940" FT /id="VSP_006764" FT VARIANT 543 FT /note="A -> S (in dbSNP:rs4151060)" FT /id="VAR_022027" FT VARIANT 592 FT /note="P -> H (in dbSNP:rs2270439)" FT /id="VAR_020119" FT MUTAGEN 307 FT /note="Y->A: Abolished binding to TFE3 and MITF FT substrates." FT /evidence="ECO:0000269|PubMed:36608670" FT MUTAGEN 321 FT /note="R->A: Abolished binding to TFE3 and MITF FT substrates." FT /evidence="ECO:0000269|PubMed:36608670" FT MUTAGEN 510 FT /note="R->A: Abolished binding to DEPTOR, TFE3 and MITF FT substrates." FT /evidence="ECO:0000269|PubMed:22017875, FT ECO:0000269|PubMed:36608670" FT HELIX 129..141 FT /evidence="ECO:0007829|PDB:2P64" FT HELIX 146..158 FT /evidence="ECO:0007829|PDB:2P64" FT HELIX 162..172 FT /evidence="ECO:0007829|PDB:2P64" FT HELIX 173..175 FT /evidence="ECO:0007829|PDB:2P64" FT HELIX 180..186 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 190..198 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 202..209 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 213..221 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 224..235 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 237..246 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 248..251 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 265..288 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 292..297 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 301..303 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 306..311 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 313..320 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 325..329 FT /evidence="ECO:0007829|PDB:6M90" FT TURN 330..332 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 335..339 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 346..351 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 353..360 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 363..369 FT /evidence="ECO:0007829|PDB:6M90" FT TURN 370..372 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 375..380 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 386..392 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 395..400 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 405..412 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 415..422 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 429..434 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 436..443 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 448..452 FT /evidence="ECO:0007829|PDB:6M90" FT TURN 453..455 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 458..462 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 469..475 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 478..483 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 488..492 FT /evidence="ECO:0007829|PDB:6M90" FT TURN 493..495 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 498..502 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 509..514 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 516..523 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 526..532 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 533..536 FT /evidence="ECO:0007829|PDB:6M90" FT HELIX 543..545 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 546..552 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 558..563 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 565..572 FT /evidence="ECO:0007829|PDB:6M90" FT STRAND 575..581 FT /evidence="ECO:0007829|PDB:6M90" SQ SEQUENCE 605 AA; 68867 MW; 4C67F3B7E400FD37 CRC64; MDPAEAVLQE KALKFMCSMP RSLWLGCSSL ADSMPSLRCL YNPGTGALTA FQNSSEREDC NNGEPPRKII PEKNSLRQTY NSCARLCLNQ ETVCLASTAM KTENCVAKTK LANGTSSMIV PKQRKLSASY EKEKELCVKY FEQWSESDQV EFVEHLISQM CHYQHGHINS YLKPMLQRDF ITALPARGLD HIAENILSYL DAKSLCAAEL VCKEWYRVTS DGMLWKKLIE RMVRTDSLWR GLAERRGWGQ YLFKNKPPDG NAPPNSFYRA LYPKIIQDIE TIESNWRCGR HSLQRIHCRS ETSKGVYCLQ YDDQKIVSGL RDNTIKIWDK NTLECKRILT GHTGSVLCLQ YDERVIITGS SDSTVRVWDV NTGEMLNTLI HHCEAVLHLR FNNGMMVTCS KDRSIAVWDM ASPTDITLRR VLVGHRAAVN VVDFDDKYIV SASGDRTIKV WNTSTCEFVR TLNGHKRGIA CLQYRDRLVV SGSSDNTIRL WDIECGACLR VLEGHEELVR CIRFDNKRIV SGAYDGKIKV WDLVAALDPR APAGTLCLRT LVEHSGRVFR LQFDEFQIVS SSHDDTILIW DFLNDPAAQA EPPRSPSRTY TYISR //