ID FBX5_HUMAN Reviewed; 447 AA. AC Q9UKT4; B3KNX5; Q5TF47; Q8WV29; Q9UGC8; DT 01-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 184. DE RecName: Full=F-box only protein 5 {ECO:0000305}; DE AltName: Full=Early mitotic inhibitor 1 {ECO:0000303|PubMed:15148369}; GN Name=FBXO5 {ECO:0000312|HGNC:HGNC:13584}; GN Synonyms=EMI1 {ECO:0000303|PubMed:11988738}, FBX5 GN {ECO:0000312|HGNC:HGNC:13584}; 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). 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] (ISOFORM 1), FUNCTION, INTERACTION WITH FZR1 AND RP CDC20, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INDUCTION. RX PubMed=11988738; DOI=10.1038/ncb785; RA Hsu J.Y., Reimann J.D.R., Sorensen C.S., Lukas J., Jackson P.K.; RT "E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting RT APC(Cdh1)."; RL Nat. Cell Biol. 4:358-366(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLU-107. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-107. RC TISSUE=Placenta; 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 [7] RP INTERACTION WITH BTRC, PHOSPHORYLATION, DEGRADATION, AND MUTAGENESIS OF RP SER-145; SER-149 AND SER-182. 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 [8] RP SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION, AND MUTAGENESIS OF RP GLU-143; SER-145; SER-148 AND SER-149. RX PubMed=15469984; DOI=10.1091/mbc.e04-07-0598; RA Hansen D.V., Loktev A.V., Ban K.H., Jackson P.K.; RT "Plk1 regulates activation of the anaphase promoting complex by RT phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC RT inhibitor Emi1."; RL Mol. Biol. Cell 15:5623-5634(2004). RN [9] RP PHOSPHORYLATION, UBIQUITINATION, AND MUTAGENESIS OF SER-145 AND SER-149. RX PubMed=15148369; DOI=10.1073/pnas.0402442101; RA Moshe Y., Boulaire J., Pagano M., Hershko A.; RT "Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, RT a regulator of the anaphase promoting complex/cyclosome."; RL Proc. Natl. Acad. Sci. U.S.A. 101:7937-7942(2004). RN [10] RP INTERACTION WITH EVI5, AND MUTAGENESIS OF 210-LYS--ASP-216. RX PubMed=16439210; DOI=10.1016/j.cell.2005.10.038; RA Eldridge A.G., Loktev A.V., Hansen D.V., Verschuren E.W., Reimann J.D.R., RA Jackson P.K.; RT "The evi5 oncogene regulates cyclin accumulation by stabilizing the RT anaphase-promoting complex inhibitor emi1."; RL Cell 124:367-380(2006). RN [11] RP FUNCTION, MUTAGENESIS OF CYS-401, AND INTERACTION WITH APC AND FZR1. RX PubMed=16921029; DOI=10.1101/gad.1454006; RA Miller J.J., Summers M.K., Hansen D.V., Nachury M.V., Lehman N.L., RA Loktev A., Jackson P.K.; RT "Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as RT a pseudosubstrate inhibitor."; RL Genes Dev. 20:2410-2420(2006). RN [12] RP FUNCTION. RX PubMed=17234884; DOI=10.1101/gad.1495007; RA Machida Y.J., Dutta A.; RT "The APC/C inhibitor, Emi1, is essential for prevention of rereplication."; RL Genes Dev. 21:184-194(2007). RN [13] RP INDUCTION, MUTAGENESIS OF ASP-144; SER-145; GLY-146 AND SER-149, AND RP FUNCTION. RX PubMed=17485488; DOI=10.1083/jcb.200611166; RA Di Fiore B., Pines J.; RT "Emi1 is needed to couple DNA replication with mitosis but does not RT regulate activation of the mitotic APC/C."; RL J. Cell Biol. 177:425-437(2007). RN [14] RP FUNCTION. RX PubMed=17875940; DOI=10.1128/mcb.00908-07; RA Verschuren E.W., Ban K.H., Masek M.A., Lehman N.L., Jackson P.K.; RT "Loss of Emi1-dependent anaphase-promoting complex/cyclosome inhibition RT deregulates E2F target expression and elicits DNA damage-induced RT senescence."; RL Mol. Cell. Biol. 27:7955-7965(2007). RN [15] RP INDUCTION. RX PubMed=19211842; DOI=10.1091/mbc.e08-08-0818; RA Lee J., Kim J.A., Barbier V., Fotedar A., Fotedar R.; RT "DNA damage triggers p21WAF1-dependent Emi1 down-regulation that maintains RT G2 arrest."; RL Mol. Biol. Cell 20:1891-1902(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP INTERACTION WITH ANAPC2; CDC23; CDC27; GMNN; UBE2S AND FZR1, FUNCTION, RP MUTAGENESIS OF 322-ARG--LEU-325; CYS-401; CYS-406 AND 444-LEU-ARG-445, AND RP REGION. RX PubMed=23708001; DOI=10.1038/ncb2755; RA Wang W., Kirschner M.W.; RT "Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase- RT promoting complex."; RL Nat. Cell Biol. 15:797-806(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP INDUCTION, AND FUNCTION. RX PubMed=29850565; DOI=10.1155/2018/7849294; RA Liu L., Liu K., Yan Y., Chu Z., Tang Y., Tang C.; RT "Two Transcripts of FBXO5 Promote Migration and Osteogenic Differentiation RT of Human Periodontal Ligament Mesenchymal Stem Cells."; RL Biomed. Res. Int. 2018:7849294-7849294(2018). RN [20] RP FUNCTION, INDUCTION, MUTAGENESIS OF CYS-401, AND UBIQUITINATION. RX PubMed=29875408; DOI=10.1038/s41586-018-0199-7; RA Cappell S.D., Mark K.G., Garbett D., Pack L.R., Rape M., Meyer T.; RT "EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start RT the cell cycle."; RL Nature 558:313-317(2018). RN [21] {ECO:0007744|PDB:2M6N} RP STRUCTURE BY NMR OF 364-447, STRUCTURE BY ELECTRON MICROSCOPY WITH APC RP COMPLEX, FUNCTION, MUTAGENESIS OF 322-ARG--LEU-325; 339-LYS--LEU-345; RP LEU-345; 346-SER--THR-355; 356-TYR--ARG-358; TYR-356; ARG-358; LEU-375; RP LYS-376; ARG-393 AND CYS-409, AND REGION. RX PubMed=23708605; DOI=10.1038/nsmb.2593; RA Frye J.J., Brown N.G., Petzold G., Watson E.R., Grace C.R., Nourse A., RA Jarvis M.A., Kriwacki R.W., Peters J.M., Stark H., Schulman B.A.; RT "Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal RT mechanism of E3 ligase shutdown."; RL Nat. Struct. Mol. Biol. 20:827-835(2013). RN [22] {ECO:0007744|PDB:4UI9} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 1-447 AND 1-23 IN RP COMPLEX WITH APC, AND SUBUNIT. RX PubMed=26083744; DOI=10.1038/nature14471; RA Chang L., Zhang Z., Yang J., McLaughlin S.H., Barford D.; RT "Atomic structure of the APC/C and its mechanism of protein RT ubiquitination."; RL Nature 522:450-454(2015). CC -!- FUNCTION: Regulator of APC activity during mitotic and meiotic cell CC cycle (PubMed:17485488, PubMed:17234884, PubMed:17875940, CC PubMed:23708001, PubMed:23708605, PubMed:16921029). During mitotic cell CC cycle plays a role as both substrate and inhibitor of APC-FZR1 complex CC (PubMed:29875408, PubMed:17485488, PubMed:17234884, PubMed:17875940, CC PubMed:23708001, PubMed:23708605, PubMed:16921029). During G1 phase, CC plays a role as substrate of APC-FZR1 complex E3 ligase CC (PubMed:29875408). Then switches as an inhibitor of APC-FZR1 complex CC during S and G2 leading to cell-cycle commitment (PubMed:29875408). As CC APC inhibitor, prevents the degradation of APC substrates at multiple CC levels: by interacting with APC and blocking access of APC substrates CC to the D-box coreceptor, formed by FZR1 and ANAPC10; by suppressing CC ubiquitin ligation and chain elongation by APC by preventing the UBE2C CC and UBE2S activities (PubMed:23708605, PubMed:23708001, CC PubMed:16921029). Plays a role in genome integrity preservation by CC coordinating DNA replication with mitosis through APC inhibition in CC interphase to stabilize CCNA2 and GMNN in order to promote mitosis and CC prevent rereplication and DNA damage-induced cellular senescence CC (PubMed:17234884, PubMed:17485488, PubMed:17875940). During oocyte CC maturation, plays a role in meiosis through inactivation of APC-FZR1 CC complex. Inhibits APC through RPS6KA2 interaction that increases FBXO5 CC affiniy for CDC20 leading to the metaphase arrest of the second meiotic CC division before fertilization (By similarity). Controls entry into the CC first meiotic division through inactivation of APC-FZR1 complex (By CC similarity). Promotes migration and osteogenic differentiation of CC mesenchymal stem cells (PubMed:29850565). CC {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:16921029, CC ECO:0000269|PubMed:17234884, ECO:0000269|PubMed:17485488, CC ECO:0000269|PubMed:17875940, ECO:0000269|PubMed:23708001, CC ECO:0000269|PubMed:23708605, ECO:0000269|PubMed:29850565, CC ECO:0000269|PubMed:29875408}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex (By CC similarity). Interacts with BTRC; mediates proteolysis by the SCF CC ubiquitin ligase complex leading to activation of APC in late mitosis CC and subsequent mitotic progression (PubMed:12791267). Interacts with CC FZR1/CDH1 and the N-terminal substrate-binding domain of CDC20; CC prevents APC activation (PubMed:11988738). Also interacts with EVI5 CC which blocks its phosphorylation by PLK1 and prevents its subsequent CC binding to BTRC and degradation (PubMed:16439210). Interacts CC simultaneously with anaphase promoting complex (APC), through at least CC ANAPC2, CDC23, CDC27, the APC substrate GMNN and the APC activator FZR1 CC (PubMed:23708001, PubMed:26083744). Interacts with UBE2S; interferes CC with the activity of UBE2S mainly by disrupting the dynamic CC electrostatic association between the C-terminal tail of UBE2S and CC ANAPC2 (PubMed:23708001). Interacts with RPS6KA2; cooperates to induce CC the metaphase arrest of early blastomeres; increases and stabilizes CC interaction of FBXO5 with CDC20 (By similarity). CC {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:11988738, CC ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:16439210, CC ECO:0000269|PubMed:23708001, ECO:0000269|PubMed:26083744}. CC -!- INTERACTION: CC Q9UKT4; P30260: CDC27; NbExp=2; IntAct=EBI-852298, EBI-994813; CC Q9UKT4; O60447: EVI5; NbExp=6; IntAct=EBI-852298, EBI-852291; CC Q9UKT4; P63208: SKP1; NbExp=5; IntAct=EBI-852298, EBI-307486; CC Q9UKT4-1; Q9UJX6: ANAPC2; NbExp=7; IntAct=EBI-16059332, EBI-396211; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11988738}. Cytoplasm CC {ECO:0000269|PubMed:11988738}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000269|PubMed:15469984}. Note=In interphase, localizes in a CC punctate manner in the nucleus and cytoplasm with some perinuclear CC concentration (PubMed:11988738). In mitotic cells, localizes throughout CC the cell, particularly at the spindle (PubMed:15469984). CC {ECO:0000269|PubMed:11988738, ECO:0000269|PubMed:15469984}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UKT4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UKT4-2; Sequence=VSP_041362; CC -!- DEVELOPMENTAL STAGE: Accumulates in late G1 phase, levels rise during S CC phase and drop in early mitosis. {ECO:0000269|PubMed:11988738}. CC -!- INDUCTION: Up-regulated at 7 days after osteogenic induction CC (PubMed:29850565). Down-regulated in late G2 phase or mitosis CC (PubMed:17485488). Down-regulated in G2 phase after DNA damage in a CC CDKN1A-dependent manner (PubMed:19211842). Down-regulated in G1 phase CC when APC-FZR1 complex is active and accumulates at the G1-S transition, CC coincident with the inactivation of APC-FZR1 complex (PubMed:29875408). CC At the G1-S transition, transcriptionally induced by the E2F CC transcription factor (PubMed:11988738). {ECO:0000269|PubMed:11988738, CC ECO:0000269|PubMed:17485488, ECO:0000269|PubMed:19211842, CC ECO:0000269|PubMed:29850565, ECO:0000269|PubMed:29875408}. CC -!- PTM: Phosphorylation by CDK2 and subsequently by PLK1 triggers CC degradation during early mitosis through ubiquitin-mediated proteolysis CC by the SCF ubiquitin ligase complex containing the F-box protein BTRC. CC This degradation is necessary for the activation of APC in late mitosis CC and subsequent mitotic progression (PubMed:12791267, PubMed:15469984). CC Phosphorylated by RPS6KA2; increases and stabilizes interaction with CC CDC20 (By similarity). {ECO:0000250|UniProtKB:Q7TSG3, CC ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:15469984}. CC -!- PTM: Ubiquitinated by the SCF(BTRC) complex following phosphorylation CC by PLK1 (PubMed:15469984). Undergoes both 'Lys-11' and 'Lys-48'-linked CC polyubiquitination by APC-FZR1 complex leading to degradation by CC proteasome during G1 phase (PubMed:29875408). Degraded through the CC SCF(BTRC) complex; degradation occurs during oocyte maturation, between CC germinal vesicle breakdown (GVBD) and meiosis I, and is required for CC the meiosis I-meiosis II transition (By similarity). CC {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:15469984, CC ECO:0000269|PubMed:29875408}. 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; AF129535; AAF04469.1; -; mRNA. DR EMBL; AY079515; AAL86610.1; -; mRNA. DR EMBL; AK055221; BAG51487.1; -; mRNA. DR EMBL; AL080276; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW47719.1; -; Genomic_DNA. DR EMBL; BC018905; AAH18905.1; -; mRNA. DR CCDS; CCDS47501.1; -. [Q9UKT4-2] DR CCDS; CCDS5242.1; -. [Q9UKT4-1] DR RefSeq; NP_001135994.1; NM_001142522.2. [Q9UKT4-2] DR RefSeq; NP_036309.1; NM_012177.4. [Q9UKT4-1] DR PDB; 2M6N; NMR; -; A=364-447. DR PDB; 4UI9; EM; 3.60 A; S=1-447, U=1-27. DR PDB; 7QE7; EM; 2.90 A; S=1-447. DR PDBsum; 2M6N; -. DR PDBsum; 4UI9; -. DR PDBsum; 7QE7; -. DR AlphaFoldDB; Q9UKT4; -. DR BMRB; Q9UKT4; -. DR EMDB; EMD-13931; -. DR SMR; Q9UKT4; -. DR BioGRID; 117655; 59. DR ComplexPortal; CPX-7904; SCF E3 ubiquitin ligase complex, FBXO5 variant. DR DIP; DIP-38023N; -. DR ELM; Q9UKT4; -. DR IntAct; Q9UKT4; 26. DR MINT; Q9UKT4; -. DR STRING; 9606.ENSP00000229758; -. DR GlyGen; Q9UKT4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UKT4; -. DR PhosphoSitePlus; Q9UKT4; -. DR BioMuta; FBXO5; -. DR DMDM; 24636847; -. DR EPD; Q9UKT4; -. DR jPOST; Q9UKT4; -. DR MassIVE; Q9UKT4; -. DR MaxQB; Q9UKT4; -. DR PaxDb; 9606-ENSP00000229758; -. DR PeptideAtlas; Q9UKT4; -. DR ProteomicsDB; 84847; -. [Q9UKT4-1] DR ProteomicsDB; 84848; -. [Q9UKT4-2] DR Pumba; Q9UKT4; -. DR Antibodypedia; 33385; 280 antibodies from 30 providers. DR DNASU; 26271; -. DR Ensembl; ENST00000229758.8; ENSP00000229758.3; ENSG00000112029.10. [Q9UKT4-1] DR Ensembl; ENST00000367241.3; ENSP00000356210.3; ENSG00000112029.10. [Q9UKT4-2] DR GeneID; 26271; -. DR KEGG; hsa:26271; -. DR MANE-Select; ENST00000229758.8; ENSP00000229758.3; NM_012177.5; NP_036309.1. DR UCSC; uc003qpg.4; human. [Q9UKT4-1] DR AGR; HGNC:13584; -. DR CTD; 26271; -. DR DisGeNET; 26271; -. DR GeneCards; FBXO5; -. DR HGNC; HGNC:13584; FBXO5. DR HPA; ENSG00000112029; Group enriched (bone marrow, lymphoid tissue). DR MIM; 606013; gene. DR neXtProt; NX_Q9UKT4; -. DR OpenTargets; ENSG00000112029; -. DR PharmGKB; PA28045; -. DR VEuPathDB; HostDB:ENSG00000112029; -. DR eggNOG; ENOG502QPWN; Eukaryota. DR GeneTree; ENSGT00530000063692; -. DR HOGENOM; CLU_055946_0_0_1; -. DR InParanoid; Q9UKT4; -. DR OMA; YVMFRTA; -. DR OrthoDB; 3089336at2759; -. DR PhylomeDB; Q9UKT4; -. DR TreeFam; TF101170; -. DR PathwayCommons; Q9UKT4; -. DR Reactome; R-HSA-174113; SCF-beta-TrCP mediated degradation of Emi1. DR Reactome; R-HSA-176408; Regulation of APC/C activators between G1/S and early anaphase. DR Reactome; R-HSA-176417; Phosphorylation of Emi1. DR Reactome; R-HSA-68881; Mitotic Metaphase/Anaphase Transition. DR Reactome; R-HSA-69205; G1/S-Specific Transcription. DR SignaLink; Q9UKT4; -. DR SIGNOR; Q9UKT4; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 26271; 762 hits in 1207 CRISPR screens. DR ChiTaRS; FBXO5; human. DR GeneWiki; FBXO5; -. DR GenomeRNAi; 26271; -. DR Pharos; Q9UKT4; Tbio. DR PRO; PR:Q9UKT4; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9UKT4; Protein. DR Bgee; ENSG00000112029; Expressed in ventricular zone and 142 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0072687; C:meiotic spindle; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IDA:UniProtKB. DR GO; GO:0010997; F:anaphase-promoting complex binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140678; F:molecular function inhibitor activity; IDA:DisProt. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; IDA:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. DR GO; GO:0046785; P:microtubule polymerization; IEA:Ensembl. DR GO; GO:2000773; P:negative regulation of cellular senescence; IMP:UniProtKB. DR GO; GO:0032876; P:negative regulation of DNA endoreduplication; IMP:UniProtKB. DR GO; GO:0045835; P:negative regulation of meiotic nuclear division; IBA:GO_Central. DR GO; GO:0045841; P:negative regulation of mitotic metaphase/anaphase transition; IDA:UniProtKB. DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl. DR GO; GO:0070169; P:positive regulation of biomineral tissue development; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:1905322; P:positive regulation of mesenchymal stem cell migration; IMP:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway. DR GO; GO:0006275; P:regulation of DNA replication; IMP:UniProtKB. DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0007088; P:regulation of mitotic nuclear division; IBA:GO_Central. DR GO; GO:0007057; P:spindle assembly involved in female meiosis I; IEA:Ensembl. DR GO; GO:0016050; P:vesicle organization; IEA:Ensembl. DR CDD; cd20364; BRcat_RBR_FBXO5; 1. DR CDD; cd22170; F-box_FBXO5; 1. DR DisProt; DP01450; -. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 2.20.25.20; -; 1. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR047147; FBX5_43. DR InterPro; IPR044064; ZF_ZBR. DR PANTHER; PTHR15493:SF8; F-BOX ONLY PROTEIN 5; 1. DR PANTHER; PTHR15493; F-BOX ONLY PROTEIN 5 AND 43; 1. DR Pfam; PF00646; F-box; 1. DR PROSITE; PS51872; ZF_ZBR; 1. DR Genevisible; Q9UKT4; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Cytoplasm; KW Cytoskeleton; Metal-binding; Mitosis; Nucleus; Phosphoprotein; KW Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc; KW Zinc-finger. FT CHAIN 1..447 FT /note="F-box only protein 5" FT /id="PRO_0000119881" FT DOMAIN 250..296 FT /note="F-box" FT ZN_FING 374..422 FT /note="ZBR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT REGION 135..244 FT /note="Interaction with EVI5" FT /evidence="ECO:0000269|PubMed:16439210" FT REGION 261..409 FT /note="Requires for efficient binding to CDC20" FT /evidence="ECO:0000250|UniProtKB:Q7TSG3" FT REGION 261..339 FT /note="Sufficient for interaction with RPS6KA2; Prevents FT association of CDC20 with RPS6KA2" FT /evidence="ECO:0000250|UniProtKB:Q7TSG3" FT REGION 305..447 FT /note="Inhibits APC ubiquitin ligase activity" FT /evidence="ECO:0000269|PubMed:23708605" FT REGION 322..325 FT /note="Competitively blocks access of APC substrates to the FT D-box coreceptor formed by FZR1 and ANAPC10" FT /evidence="ECO:0000269|PubMed:23708001" FT REGION 337..358 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 378..420 FT /note="Allows a rapid multiple mono-ubiquitination of the FT APC substrate, but strongly inhibits the slow ubiquitin FT chain elongation catalyzed by UBCH10" FT /evidence="ECO:0000269|PubMed:23708001" FT REGION 437..447 FT /note="Sufficient to suppress UBE2S activity; essential for FT interaction with UBE2S; competitively inhibits the rapide FT ubiquitin chain elongation by UBE2D1 which blocks UBE2D1 FT with APC; indispensable for recruitment and position of FT FBXO5 to the catalytic site of APC; abrogates the FT inhibition of ubiquitin chain assembly primarily catalyzed FT by UBE2S; inhibits the ubiquitination by either UBE2C or FT UBE2D1" FT /evidence="ECO:0000269|PubMed:23708001" FT BINDING 378 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 381 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 396 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 401 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 406 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 409 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 414 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT BINDING 419 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220" FT MOD_RES 94 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q7TSG3" FT MOD_RES 102 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..46 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041362" FT VARIANT 107 FT /note="Q -> E (in dbSNP:rs2073260)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_024440" FT VARIANT 164 FT /note="L -> F (in dbSNP:rs7763565)" FT /id="VAR_049038" FT MUTAGEN 143 FT /note="E->A: Delays degradation." FT /evidence="ECO:0000269|PubMed:15469984" FT MUTAGEN 144 FT /note="D->A: Does not affect protein stability." FT /evidence="ECO:0000269|PubMed:17485488" FT MUTAGEN 145 FT /note="S->A: Does not affect protein stability; when FT associated with A-149." FT /evidence="ECO:0000269|PubMed:17485488" FT MUTAGEN 145 FT /note="S->E: Degraded in similar manner to wild-type." FT /evidence="ECO:0000269|PubMed:12791267, FT ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984" FT MUTAGEN 145 FT /note="S->N: Not mitotically degraded. Shows impaired FT interaction with BTRC and reduced phosphate incorporation; FT when associated with N-149." FT /evidence="ECO:0000269|PubMed:12791267, FT ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984" FT MUTAGEN 146 FT /note="G->V: Does not affect protein stability." FT /evidence="ECO:0000269|PubMed:17485488" FT MUTAGEN 148 FT /note="S->A: Degraded in similar manner to wild-type." FT /evidence="ECO:0000269|PubMed:15469984" FT MUTAGEN 149 FT /note="S->A: Does not affect protein stability; when FT associated with A-145." FT /evidence="ECO:0000269|PubMed:17485488" FT MUTAGEN 149 FT /note="S->E: Degraded in similar manner to wild-type." FT /evidence="ECO:0000269|PubMed:12791267, FT ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984" FT MUTAGEN 149 FT /note="S->N: Not mitotically degraded. Shows impaired FT interaction with BTRC and reduced phosphate incorporation; FT when associated with N-145." FT /evidence="ECO:0000269|PubMed:12791267, FT ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984" FT MUTAGEN 182 FT /note="S->A: Shows impaired interaction with BTRC." FT /evidence="ECO:0000269|PubMed:12791267" FT MUTAGEN 210..216 FT /note="KRNPKVD->AAAAAAA: Loss of interaction with EVI5." FT /evidence="ECO:0000269|PubMed:16439210" FT MUTAGEN 322..325 FT /note="RTPL->ATPA: Does not affect inhibition of FT UBE2S-catalyzed chain elongation. Efficiently inhibits the FT degradation of PTTG1 at relatively high concentration. FT Reduces the competitive ability of FBXO5 to inhibit the FT association of PTTG1 to APC. Cannot compete with the APC FT substrate for APC binding. Decreases inhibition of CCNB1 FT ubiquitination by UBE2C." FT /evidence="ECO:0000269|PubMed:23708001, FT ECO:0000269|PubMed:23708605" FT MUTAGEN 339..345 FT /note="Missing: Impairs CCNB1 ubiquitination by UBE2C; when FT associated with 356-Y--R-358 del." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 345 FT /note="L->A: Substantially impairs inhibition of CCNB1 FT ubiquitination by UBE2C; when associated with 346-S--T-355 FT del." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 346..355 FT /note="Missing: Inhibits CCNB1 ubiquitination by UBE2C. FT Substantially impairs inhibition of CCNB1 ubiquitination by FT UBE2C; when associated with A-345; A-356 and A-358." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 356..358 FT /note="Missing: Impairs CCNB1 ubiquitination by UBE2C; when FT associated with 339-K--L-345 del." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 356 FT /note="Y->A: Substantially impairs inhibition of CCNB1 FT ubiquitination by UBE2C; when associated with 346-S--T-355 FT del." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 358 FT /note="R->A: Substantially impairs inhibition of CCNB1 FT ubiquitination by UBE2C; when associated with 346-S--T-355 FT del." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 375 FT /note="L->A: Decreases UBE2C-mediated ubiquitination." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 376 FT /note="K->A: Decreases UBE2C-mediated ubiquitination." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 393 FT /note="R->A: Decreases UBE2C-mediated ubiquitination." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 401 FT /note="C->S: Reduced inhibition of APC. Does not affect the FT FBXO5-mediated inhibitory activity against ubiquitin chain FT assembly. Does not affect the FBXO5-mediated inhibitory FT activity against ubiquitin chain assembly; when associated FT with S-401. Does not affect inhibition of UBE2S-catalyzed FT chain elongation. Reduces the competitive ability of FBXO5 FT to inhibit the association of securin to APC. Can still FT compete with the APC substrate for APC binding. Fails to FT inhibit ubiquitin chain assembly by UBE2C or FT mono-ubiquitination by UBE2D1. Largely abolishes the FT inhibitory activity against protein degradation. Fails to FT inactivate APC-FZR1 complex. Allows FBXO5 degradation in FT the absence of CDK4 inhibitor." FT /evidence="ECO:0000269|PubMed:16921029, FT ECO:0000269|PubMed:23708001, ECO:0000269|PubMed:29875408" FT MUTAGEN 406 FT /note="C->S: Does not affect the inhibitory activity FT against chain assembly; when associated with S-401." FT /evidence="ECO:0000269|PubMed:23708001" FT MUTAGEN 409 FT /note="C->A: Decreases UBE2C-mediated ubiquitination." FT /evidence="ECO:0000269|PubMed:23708605" FT MUTAGEN 444..445 FT /note="LR->AA: Loses inhibitory activity on UBE2S-catalyzed FT chain elongation." FT /evidence="ECO:0000269|PubMed:23708001" FT CONFLICT 212 FT /note="N -> D (in Ref. 3; BAG51487)" FT /evidence="ECO:0000305" FT HELIX 359..367 FT /evidence="ECO:0007829|PDB:7QE7" FT STRAND 374..377 FT /evidence="ECO:0007829|PDB:7QE7" FT TURN 379..381 FT /evidence="ECO:0007829|PDB:7QE7" FT STRAND 383..388 FT /evidence="ECO:0007829|PDB:7QE7" FT TURN 389..392 FT /evidence="ECO:0007829|PDB:7QE7" FT STRAND 393..395 FT /evidence="ECO:0007829|PDB:7QE7" FT STRAND 404..406 FT /evidence="ECO:0007829|PDB:2M6N" FT TURN 407..409 FT /evidence="ECO:0007829|PDB:7QE7" FT STRAND 410..412 FT /evidence="ECO:0007829|PDB:2M6N" FT STRAND 415..417 FT /evidence="ECO:0007829|PDB:7QE7" FT HELIX 438..446 FT /evidence="ECO:0007829|PDB:7QE7" SQ SEQUENCE 447 AA; 50146 MW; 196FBC2578F92120 CRC64; MSRRPCSCAL RPPRCSCSAS PSAVTAAGRP RPSDSCKEES STLSVKMKCD FNCNHVHSGL KLVKPDDIGR LVSYTPAYLE GSCKDCIKDY ERLSCIGSPI VSPRIVQLET ESKRLHNKEN QHVQQTLNST NEIEALETSR LYEDSGYSSF SLQSGLSEHE EGSLLEENFG DSLQSCLLQI QSPDQYPNKN LLPVLHFEKV VCSTLKKNAK RNPKVDREML KEIIARGNFR LQNIIGRKMG LECVDILSEL FRRGLRHVLA TILAQLSDMD LINVSKVSTT WKKILEDDKG AFQLYSKAIQ RVTENNNKFS PHASTREYVM FRTPLASVQK SAAQTSLKKD AQTKLSNQGD QKGSTYSRHN EFSEVAKTLK KNESLKACIR CNSPAKYDCY LQRATCKREG CGFDYCTKCL CNYHTTKDCS DGKLLKASCK IGPLPGTKKS KKNLRRL //