FBX5_MOUSE
ID FBX5_MOUSE Reviewed; 421 AA.
AC Q7TSG3;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=F-box only protein 5 {ECO:0000305};
DE AltName: Full=Early mitotic inhibitor 1 {ECO:0000250|UniProtKB:Q9UKT4};
GN Name=Fbxo5 {ECO:0000312|MGI:MGI:1914391};
GN Synonyms=Emi1 {ECO:0000303|PubMed:16809773};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:AAH53434.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH53434.1};
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 [2]
RP INTERACTION WITH RPS6KA2 AND CDC20, TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, REGION, PHOSPHORYLATION, MUTAGENESIS OF SER-284; THR-289; THR-342
RP AND SER-348, AND FUNCTION.
RX PubMed=15526037; DOI=10.1038/sj.emboj.7600448;
RA Paronetto M.P., Giorda E., Carsetti R., Rossi P., Geremia R., Sette C.;
RT "Functional interaction between p90Rsk2 and Emi1 contributes to the
RT metaphase arrest of mouse oocytes.";
RL EMBO J. 23:4649-4659(2004).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16809773; DOI=10.1128/mcb.00043-06;
RA Lee H., Lee D.J., Oh S.P., Park H.D., Nam H.H., Kim J.M., Lim D.-S.;
RT "Mouse emi1 has an essential function in mitotic progression during early
RT embryogenesis.";
RL Mol. Cell. Biol. 26:5373-5381(2006).
RN [4]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, PROTEOLYSIS DEGRADATION, AND
RP FUNCTION.
RX PubMed=17190794; DOI=10.1083/jcb.200607070;
RA Marangos P., Verschuren E.W., Chen R., Jackson P.K., Carroll J.;
RT "Prophase I arrest and progression to metaphase I in mouse oocytes are
RT controlled by Emi1-dependent regulation of APC(Cdh1).";
RL J. Cell Biol. 176:65-75(2007).
RN [5]
RP TISSUE SPECIFICITY.
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Regulator of APC activity during mitotic and meiotic cell
CC cycle (PubMed:17190794, PubMed:15526037, PubMed:16809773). During
CC mitotic cell cycle plays a role as both substrate and inhibitor of APC-
CC FZR1 complex (PubMed:16809773). During G1 phase, plays a role as
CC substrate of APC-FZR1 complex E3 ligase. Then switches as an inhibitor
CC of APC-FZR1 complex during S and G2 leading to cell-cycle commitment.
CC As APC inhibitor, prevents the degradation of APC substrates at
CC multiple levels: by interacting with APC and blocking access of APC
CC substrates to the D-box co-receptor, formed by FZR1 and ANAPC10; by
CC suppressing ubiquitin ligation and chain elongation by APC by
CC preventing the UBE2C and UBE2S activities. Plays a role in genome
CC integrity preservation by coordinating DNA replication with mitosis
CC through APC inhibition in interphase to stabilize CCNA2 and GMNN in
CC order to promote mitosis and prevent rereplication and DNA damage-
CC induced cellular senescence (By similarity). During oocyte maturation,
CC plays a role in meiosis through inactivation of APC-FZR1 complex.
CC Inhibits APC through RPS6KA2 interaction that increases FBXO5 affiniy
CC for CDC20 leading to the metaphase arrest of the second meiotic
CC division before fertilization (PubMed:15526037). Controls entry into
CC the first meiotic division through inactivation of APC-FZR1 complex
CC (PubMed:17190794). Promotes migration and osteogenic differentiation of
CC mesenchymal stem cells (By similarity). {ECO:0000250|UniProtKB:Q9UKT4,
CC ECO:0000269|PubMed:15526037, ECO:0000269|PubMed:16809773,
CC ECO:0000269|PubMed:17190794}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
CC Interacts with BTRC; mediates proteolysis by the SCF ubiquitin ligase
CC complex leading to activation of APC in late mitosis and subsequent
CC mitotic progression. Interacts with FZR1/CDH1 and the N-terminal
CC substrate-binding domain of CDC20; prevents APC activation. Also
CC interacts with EVI5 which blocks its phosphorylation by PLK1 and
CC prevents its subsequent binding to BTRC and degradation. Interacts
CC simultaneously with anaphase promoting complex (APC), through at least
CC ANAPC2, CDC23, CDC27, the APC substrate GMNN and the APC activator
CC FZR1. Interacts with UBE2S; interferes with the activity of UBE2S
CC mainly by disrupting the dynamic electrostatic association between the
CC C-terminal tail of UBE2S and ANAPC2 (By similarity). Interacts with
CC RPS6KA2; cooperates to induce the metaphase arrest of early
CC blastomeres; increases and stabilizes interaction of FBXO5 with CDC20
CC (PubMed:15526037). {ECO:0000250|UniProtKB:Q9UKT4,
CC ECO:0000269|PubMed:15526037}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9UKT4}. Cytoplasm
CC {ECO:0000269|PubMed:15526037}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:15526037}. Note=In interphase, localizes in a
CC punctate manner in the nucleus and cytoplasm with some perinuclear
CC concentration. In mitotic cells, localizes throughout the cell,
CC particularly at the spindle. {ECO:0000250|UniProtKB:Q9UKT4}.
CC -!- TISSUE SPECIFICITY: Expressed in oocytes and granulosa cells
CC (PubMed:15526037, PubMed:17190794). Expressed in proliferating cells
CC compartments in hair follicle and skin epidermis, spermatogonia, and
CC intestinal crypts (PubMed:17875940). {ECO:0000269|PubMed:15526037,
CC ECO:0000269|PubMed:17190794, ECO:0000269|PubMed:17875940}.
CC -!- DEVELOPMENTAL STAGE: Detected at the germinal vesicle (GV) stage.
CC During maturation, decreases to barely detectable levels in meiosis
CC I- and meiosis II-stage oocytes. {ECO:0000269|PubMed:17190794}.
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 (By similarity). Phosphorylated by
CC RPS6KA2; increases and stabilizes interaction with CDC20
CC (PubMed:15526037). {ECO:0000250|UniProtKB:Q9UKT4,
CC ECO:0000269|PubMed:15526037}.
CC -!- PTM: Ubiquitinated by the SCF(BTRC) complex following phosphorylation
CC by PLK1. Undergoes both 'Lys-11' and 'Lys-48'-linked polyubiquitination
CC by APC-FZR1 complex leading to degradation during G1 phase by the
CC proteasome (By similarity). Degraded through the SCF(BTRC) complex;
CC degradation occurs during oocyte maturation, between germinal vesicle
CC breakdown (GVBD) and meiosis I, and is required for the meiosis I-
CC meiosis II transition (PubMed:17190794). {ECO:0000250|UniProtKB:Q9UKT4,
CC ECO:0000269|PubMed:17190794}.
CC -!- DISRUPTION PHENOTYPE: Death at the preimplantation stage. Embryos
CC display normal cell proliferation but mitotic progression is severely
CC defective during embryonic cleavage with multipolar spindles and
CC misaligned chromosomes frequently observed.
CC {ECO:0000269|PubMed:16809773}.
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DR EMBL; BC053434; AAH53434.1; -; mRNA.
DR CCDS; CCDS56683.1; -.
DR RefSeq; NP_080271.2; NM_025995.2.
DR AlphaFoldDB; Q7TSG3; -.
DR SMR; Q7TSG3; -.
DR BioGRID; 211971; 13.
DR STRING; 10090.ENSMUSP00000019907; -.
DR iPTMnet; Q7TSG3; -.
DR PhosphoSitePlus; Q7TSG3; -.
DR EPD; Q7TSG3; -.
DR jPOST; Q7TSG3; -.
DR MaxQB; Q7TSG3; -.
DR PaxDb; Q7TSG3; -.
DR PeptideAtlas; Q7TSG3; -.
DR PRIDE; Q7TSG3; -.
DR ProteomicsDB; 272972; -.
DR Antibodypedia; 33385; 245 antibodies from 29 providers.
DR DNASU; 67141; -.
DR Ensembl; ENSMUST00000019907; ENSMUSP00000019907; ENSMUSG00000019773.
DR GeneID; 67141; -.
DR KEGG; mmu:67141; -.
DR UCSC; uc007egj.1; mouse.
DR CTD; 26271; -.
DR MGI; MGI:1914391; Fbxo5.
DR VEuPathDB; HostDB:ENSMUSG00000019773; -.
DR eggNOG; ENOG502QPWN; Eukaryota.
DR GeneTree; ENSGT00530000063692; -.
DR HOGENOM; CLU_055946_0_0_1; -.
DR InParanoid; Q7TSG3; -.
DR OMA; FDFCTRC; -.
DR OrthoDB; 521317at2759; -.
DR PhylomeDB; Q7TSG3; -.
DR TreeFam; TF101170; -.
DR Reactome; R-MMU-174113; SCF-beta-TrCP mediated degradation of Emi1.
DR Reactome; R-MMU-176408; Regulation of APC/C activators between G1/S and early anaphase.
DR Reactome; R-MMU-176417; Phosphorylation of Emi1.
DR Reactome; R-MMU-68881; Mitotic Metaphase/Anaphase Transition.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 67141; 26 hits in 72 CRISPR screens.
DR ChiTaRS; Fbxo5; mouse.
DR PRO; PR:Q7TSG3; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q7TSG3; protein.
DR Bgee; ENSMUSG00000019773; Expressed in dorsal pancreas and 191 other tissues.
DR Genevisible; Q7TSG3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0072687; C:meiotic spindle; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0010997; F:anaphase-promoting complex binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0046785; P:microtubule polymerization; IDA:MGI.
DR GO; GO:2000773; P:negative regulation of cellular senescence; ISS:UniProtKB.
DR GO; GO:0032876; P:negative regulation of DNA endoreduplication; ISS:UniProtKB.
DR GO; GO:0045835; P:negative regulation of meiotic nuclear division; IDA:MGI.
DR GO; GO:0045841; P:negative regulation of mitotic metaphase/anaphase transition; ISO:MGI.
DR GO; GO:2001021; P:negative regulation of response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; IDA:MGI.
DR GO; GO:0070169; P:positive regulation of biomineral tissue development; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0060903; P:positive regulation of meiosis I; ISO:MGI.
DR GO; GO:1905322; P:positive regulation of mesenchymal stem cell migration; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0006275; P:regulation of DNA replication; ISS:UniProtKB.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IDA:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IBA:GO_Central.
DR GO; GO:0051225; P:spindle assembly; IDA:MGI.
DR GO; GO:0007057; P:spindle assembly involved in female meiosis I; IDA:MGI.
DR GO; GO:0016050; P:vesicle organization; IDA:MGI.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR044064; ZF_ZBR.
DR Pfam; PF00646; F-box; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS51872; ZF_ZBR; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cytoplasm; Cytoskeleton; Metal-binding; Mitosis;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..421
FT /note="F-box only protein 5"
FT /id="PRO_0000258008"
FT DOMAIN 223..273
FT /note="F-box"
FT /evidence="ECO:0000255"
FT ZN_FING 348..396
FT /note="ZBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT REGION 114..219
FT /note="Interaction with EVI5"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT4"
FT REGION 236..383
FT /note="Requires for efficient binding to CDC20"
FT /evidence="ECO:0000269|PubMed:15526037"
FT REGION 236..313
FT /note="Sufficient for interaction with RPS6KA2; Prevents
FT association of CDC20 with RPS6KA2"
FT /evidence="ECO:0000269|PubMed:15526037"
FT REGION 280..421
FT /note="Inhibits APC ubiquitin ligase activity"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT4"
FT REGION 296..299
FT /note="Competitively blocks access of APC substrates to the
FT D-box coreceptor formed by FZR1 and ANAPC10"
FT /evidence="ECO:0000250|UniProtKB:Q9UKT4"
FT REGION 352..394
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:0000250|UniProtKB:Q9UKT4"
FT REGION 411..421
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:0000250|UniProtKB:Q9UKT4"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 355
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 370
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT BINDING 393
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01220"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 284
FT /note="S->A: Decreases phosphorylation by RPS6KA2."
FT /evidence="ECO:0000269|PubMed:15526037"
FT MUTAGEN 289
FT /note="T->A: Decreases phosphorylation by RPS6KA2."
FT /evidence="ECO:0000269|PubMed:15526037"
FT MUTAGEN 342
FT /note="T->A: Does not affect phosphorylation by RPS6KA2."
FT /evidence="ECO:0000269|PubMed:15526037"
FT MUTAGEN 348
FT /note="S->A: Does not affect phosphorylation by RPS6KA2."
FT /evidence="ECO:0000269|PubMed:15526037"
SQ SEQUENCE 421 AA; 47508 MW; A3624DA41F8DA285 CRC64;
MSRRTCSDLR RPSSCPCRLG ARTTVDGCKE ESPVLSVTMK CFNCNPDLSE LEVVKPEDSG
IEASYSPVCL EPSCNDCVRN HERLSFIDSP IVGHDNKENQ RVQNTLDSSN ETEELEASRL
YEDSGYSSFT QSDRDDGILI LENFRNSPQA RLLPSQSPDQ HPNKTLLPVL HFERVVCSTL
KKNGKRNPKV DREMLKEVIA SGNFRLQNII GKKMGLEHLD ILAELSRRGF VHLLANILTK
LSGMDLVNLS KVSRIWKKIL ENNKGAFQLY SKTMQRVIES SKLSLHATTR GYVVGRAALT
CVQKSSTWAP PKKDVQIKSS SQRGQRVSTY SRHNEFVEVA KTLKNNESLK ACVRCNFPAK
YDHYLERAVC KRESCQFEYC TKCLCAYHNN KDCLNGKILK ASCKVGPLPG TKKSKKNLQR
L
