FBW1A_HUMAN
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 03-AUG-2022, entry version 220.
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;
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), AND FUNCTION.
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 CHARACTERIZATION.
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, AND FUNCTION IN UBIQUITINATION OF NFKB1.
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 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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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. Recognizes and binds to phosphorylated target proteins
CC (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356,
CC PubMed:11238952, PubMed:11359933, 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:22087322). 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:10066435, PubMed:10497169, PubMed:10644755).
CC Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22'
CC (PubMed:10066435). SCF(BTRC) mediates the ubiquitination of CEP68; this
CC is required for centriole separation during mitosis (PubMed:25704143,
CC PubMed:25503564). SCF(BTRC) mediates the ubiquitination and subsequent
CC degradation of nuclear NFE2L1 (By similarity). Has an essential role in
CC the control of the clock-dependent transcription via degradation of
CC phosphorylated PER1 and PER2 (PubMed:15917222). May be involved in
CC ubiquitination and subsequent proteasomal degradation through a DBB1-
CC CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-
CC mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF.
CC Required for proteolytic processing of GLI3 (PubMed:16371461). Mediates
CC ubiquitination of REST, thereby leading to its proteasomal degradation
CC (PubMed:21258371, PubMed:18354482). SCF(BTRC) mediates the
CC ubiquitination and subsequent proteasomal degradation of KLF4; thereby
CC negatively regulating cell pluripotency maintenance and embryogenesis
CC (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: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:14681206, ECO:0000269|PubMed:14988407,
CC ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15917222,
CC ECO:0000269|PubMed:16371461, ECO:0000269|PubMed:18354482,
CC ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:22087322,
CC ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143,
CC ECO:0000269|PubMed:9859996}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Self-associates. Component of the SCF(BTRC) complex
CC formed of CUL1, SKP1, RBX1 and a BTRC dimer. Direct interaction with
CC SKP1 occurs via the F-box domain. Interacts with phosphorylated
CC ubiquitination substrates SMAD3 and SMAD4. Interacts with
CC phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB,
CC NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A,
CC DLG1, FBXO5 and SNAI1; the interaction requires the phosphorylation of
CC the 2 serine residues in the substrate destruction motif D-S-G-
CC X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts
CC with FBXW11. Interacts with CUL4A and DDB1. Part of a SCF(BTRC)-like
CC complex lacking CUL1, which is associated with phosphorylated NKBIA and
CC RELA; RELA interacts directly with NFKBIA. Interacts with the
CC phosphorylated form of GLI3. Interacts with CLU. Interacts with PER1
CC (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with
CC phosphorylated ubiquitination substrate CEP68 (PubMed:25704143,
CC PubMed:25503564). Interacts with ZC3H12A; this interaction occurs when
CC ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (By
CC similarity). Interacts with HSF1; this interaction occurs during
CC mitosis and induces HSF1 ubiquitin-dependent degradation, a process
CC inhibited by CDC20 (PubMed:18794143). Interacts with NFE2L1 (By
CC 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:22087322, ECO:0000269|PubMed:25503564,
CC ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:29420262}.
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 -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BTRCID451ch10q24.html";
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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 SMR; Q9Y297; -.
DR BioGRID; 114457; 468.
DR CORUM; Q9Y297; -.
DR DIP; DIP-31607N; -.
DR IntAct; Q9Y297; 153.
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; Q9Y297; -.
DR PeptideAtlas; Q9Y297; -.
DR PRIDE; Q9Y297; -.
DR ProteomicsDB; 85705; -. [Q9Y297-1]
DR ProteomicsDB; 85706; -. [Q9Y297-2]
DR Antibodypedia; 31277; 380 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 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; ENNWRMG; -.
DR OrthoDB; 666965at2759; -.
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; 18 hits in 1127 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 178 other tissues.
DR ExpressionAtlas; Q9Y297; baseline and differential.
DR Genevisible; Q9Y297; HS.
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:ParkinsonsUK-UCL.
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:0045879; P:negative regulation of smoothened signaling pathway; TAS:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS: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: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:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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; ISS: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 Gene3D; 2.130.10.10; -; 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; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12125; Beta-TrCP_D; 1.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF00400; WD40; 6.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM01028; Beta-TrCP_D; 1.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 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.
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 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 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
