FBX5_HUMAN
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 03-AUG-2022, entry version 175.
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},
GN FBX5 {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}.
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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 SMR; Q9UKT4; -.
DR BioGRID; 117655; 55.
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; Q9UKT4; -.
DR PeptideAtlas; Q9UKT4; -.
DR PRIDE; Q9UKT4; -.
DR ProteomicsDB; 84847; -. [Q9UKT4-1]
DR ProteomicsDB; 84848; -. [Q9UKT4-2]
DR Antibodypedia; 33385; 245 antibodies from 29 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 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; FDFCTRC; -.
DR OrthoDB; 521317at2759; -.
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; 736 hits in 1127 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 141 other tissues.
DR Genevisible; Q9UKT4; HS.
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: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: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:2001021; P:negative regulation of response to DNA damage stimulus; IMP: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 DisProt; DP01450; -.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR044064; ZF_ZBR.
DR Pfam; PF00646; F-box; 1.
DR PROSITE; PS51872; ZF_ZBR; 1.
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 UBE2S-
FT 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 mono-
FT ubiquitination by UBE2D1. Largely abolishes the inhibitory
FT activity against protein degradation. Fails to inactivate
FT APC-FZR1 complex. Allows FBXO5 degradation in the absence
FT 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
