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Protein

F-box only protein 5

Gene

Fbxo5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Regulator of APC activity during mitotic and meiotic cell cycle (PubMed:17190794, PubMed:15526037, PubMed:16809773). During mitotic cell cycle plays a role as both substrate and inhibitor of APC-FZR1 complex (PubMed:16809773). During G1 phase, plays a role as substrate of APC-FZR1 complex E3 ligase. Then switches as an inhibitor of APC-FZR1 complex during S and G2 leading to cell-cycle commitment. As APC inhibitor, prevents the degradation of APC substrates at multiple levels: by interacting with APC and blocking access of APC substrates to the D-box co-receptor, formed by FZR1 and ANAPC10; by suppressing ubiquitin ligation and chain elongation by APC by preventing the UBE2C and UBE2S activities. Plays a role in genome integrity preservation by coordinating DNA replication with mitosis through APC inhibition in interphase to stabilize CCNA2 and GMNN in order to promote mitosis and prevent rereplication and DNA damage-induced cellular senescence (By similarity). During oocyte maturation, plays a role in meiosis through inactivation of APC-FZR1 complex. Inhibits APC through RPS6KA2 interaction that increases FBXO5 affiniy for CDC20 leading to the metaphase arrest of the second meiotic division before fertilization (PubMed:15526037). Controls entry into the first meiotic division through inactivation of APC-FZR1 complex (PubMed:17190794). Promotes migration and osteogenic differentiation of mesenchymal stem cells (By similarity).By similarity3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri348 – 396ZBR-typePROSITE-ProRule annotationAdd BLAST49

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Mitosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-174113 SCF-beta-TrCP mediated degradation of Emi1
R-MMU-176408 Regulation of APC/C activators between G1/S and early anaphase
R-MMU-176417 Phosphorylation of Emi1
R-MMU-68881 Mitotic Metaphase/Anaphase Transition
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
F-box only protein 5Curated
Alternative name(s):
Early mitotic inhibitor 1By similarity
Gene namesi
Name:Fbxo5Imported
Synonyms:Emi11 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1914391 Fbxo5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Disruption phenotypei

Death at the preimplantation stage. Embryos display normal cell proliferation but mitotic progression is severely defective during embryonic cleavage with multipolar spindles and misaligned chromosomes frequently observed.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi284S → A: Decreases phosphorylation by RPS6KA2. 1 Publication1
Mutagenesisi289T → A: Decreases phosphorylation by RPS6KA2. 1 Publication1
Mutagenesisi342T → A: Does not affect phosphorylation by RPS6KA2. 1 Publication1
Mutagenesisi348S → A: Does not affect phosphorylation by RPS6KA2. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002580081 – 421F-box only protein 5Add BLAST421

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei85PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation by CDK2 and subsequently by PLK1 triggers degradation during early mitosis through ubiquitin-mediated proteolysis by the SCF ubiquitin ligase complex containing the F-box protein BTRC. This degradation is necessary for the activation of APC in late mitosis and subsequent mitotic progression (By similarity). Phosphorylated by RPS6KA2; increases and stabilizes interaction with CDC20 (PubMed:15526037).By similarity1 Publication
Ubiquitinated by the SCF(BTRC) complex following phosphorylation by PLK1. Undergoes both 'Lys-11' and 'Lys-48'-linked polyubiquitination by APC-FZR1 complex leading to degradation during G1 phase by the proteasome (By similarity). Degraded through the SCF(BTRC) complex; degradation occurs during oocyte maturation, between germinal vesicle breakdown (GVBD) and meiosis I, and is required for the meiosis I-meiosis II transition (PubMed:17190794).By similarity1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ7TSG3
MaxQBiQ7TSG3
PaxDbiQ7TSG3
PeptideAtlasiQ7TSG3
PRIDEiQ7TSG3

PTM databases

iPTMnetiQ7TSG3
PhosphoSitePlusiQ7TSG3

Expressioni

Tissue specificityi

Expressed in oocytes and granulosa cells (PubMed:15526037, PubMed:17190794). Expressed in proliferating cells compartments in hair follicle and skin epidermis, spermatogonia, and intestinal crypts (PubMed:17875940).3 Publications

Developmental stagei

Detected at the germinal vesicle (GV) stage. During maturation, decreases to barely detectable levels in meiosis I- and meiosis II-stage oocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000019773 Expressed in 204 organ(s), highest expression level in dorsal pancreas
CleanExiMM_FBXO5
GenevisibleiQ7TSG3 MM

Interactioni

Subunit structurei

Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with BTRC; mediates proteolysis by the SCF ubiquitin ligase complex leading to activation of APC in late mitosis and subsequent mitotic progression. Interacts with FZR1/CDH1 and the N-terminal substrate-binding domain of CDC20; prevents APC activation. Also interacts with EVI5 which blocks its phosphorylation by PLK1 and prevents its subsequent binding to BTRC and degradation. Interacts simultaneously with anaphase promoting complex (APC), through at least ANAPC2, CDC23, CDC27, the APC substrate GMNN and the APC activator FZR1. Interacts with UBE2S; interferes with the activity of UBE2S mainly by disrupting the dynamic electrostatic association between the C-terminal tail of UBE2S and ANAPC2 (By similarity). Interacts with RPS6KA2; cooperates to induce the metaphase arrest of early blastomeres; increases and stabilizes interaction of FBXO5 with CDC20 (PubMed:15526037).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211971, 2 interactors
STRINGi10090.ENSMUSP00000019907

Structurei

3D structure databases

ProteinModelPortaliQ7TSG3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini223 – 273F-boxSequence analysisAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni114 – 219Interaction with EVI5By similarityAdd BLAST106
Regioni236 – 383Requires for efficient binding to CDC201 PublicationAdd BLAST148
Regioni236 – 313Sufficient for interaction with RPS6KA2; Prevents association of CDC20 with RPS6KA21 PublicationAdd BLAST78
Regioni280 – 421Inhibits APC ubiquitin ligase activityBy similarityAdd BLAST142
Regioni296 – 299Competitively blocks access of APC substrates to the D-box coreceptor formed by FZR1 and ANAPC10By similarity4
Regioni352 – 394Allows a rapid multiple mono-ubiquitination of the APC substrate, but strongly inhibits the slow ubiquitin chain elongation catalyzed by UBCH10By similarityAdd BLAST43
Regioni411 – 421Sufficient to suppress UBE2S activity; essential for interaction with UBE2S; competitively inhibits the rapide ubiquitin chain elongation by UBE2D1 which blocks UBE2D1 with APC; indispensable for recruitment and position of FBXO5 to the catalytic site of APC; abrogates the inhibition of ubiquitin chain assembly primarily catalyzed by UBE2S; inhibits the ubiquitination by either UBE2C or UBE2D1By similarityAdd BLAST11

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri348 – 396ZBR-typePROSITE-ProRule annotationAdd BLAST49

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJ4T Eukaryota
ENOG4111MJS LUCA
GeneTreeiENSGT00530000063692
HOGENOMiHOG000035122
HOVERGENiHBG010089
InParanoidiQ7TSG3
KOiK10292
OMAiDYCTRCL
OrthoDBiEOG091G08DI
PhylomeDBiQ7TSG3
TreeFamiTF101170

Family and domain databases

InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
PfamiView protein in Pfam
PF00646 F-box, 1 hit
SUPFAMiSSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS51872 ZF_ZBR, 1 hit

Sequencei

Sequence statusi: Complete.

Q7TSG3-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSRRTCSDLR RPSSCPCRLG ARTTVDGCKE ESPVLSVTMK CFNCNPDLSE
60 70 80 90 100
LEVVKPEDSG IEASYSPVCL EPSCNDCVRN HERLSFIDSP IVGHDNKENQ
110 120 130 140 150
RVQNTLDSSN ETEELEASRL YEDSGYSSFT QSDRDDGILI LENFRNSPQA
160 170 180 190 200
RLLPSQSPDQ HPNKTLLPVL HFERVVCSTL KKNGKRNPKV DREMLKEVIA
210 220 230 240 250
SGNFRLQNII GKKMGLEHLD ILAELSRRGF VHLLANILTK LSGMDLVNLS
260 270 280 290 300
KVSRIWKKIL ENNKGAFQLY SKTMQRVIES SKLSLHATTR GYVVGRAALT
310 320 330 340 350
CVQKSSTWAP PKKDVQIKSS SQRGQRVSTY SRHNEFVEVA KTLKNNESLK
360 370 380 390 400
ACVRCNFPAK YDHYLERAVC KRESCQFEYC TKCLCAYHNN KDCLNGKILK
410 420
ASCKVGPLPG TKKSKKNLQR L
Length:421
Mass (Da):47,508
Last modified:October 1, 2003 - v1
Checksum:iA3624DA41F8DA285
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC053434 mRNA Translation: AAH53434.1
CCDSiCCDS56683.1
RefSeqiNP_080271.2, NM_025995.2
UniGeneiMm.197520

Genome annotation databases

EnsembliENSMUST00000019907; ENSMUSP00000019907; ENSMUSG00000019773
GeneIDi67141
KEGGimmu:67141
UCSCiuc007egj.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC053434 mRNA Translation: AAH53434.1
CCDSiCCDS56683.1
RefSeqiNP_080271.2, NM_025995.2
UniGeneiMm.197520

3D structure databases

ProteinModelPortaliQ7TSG3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211971, 2 interactors
STRINGi10090.ENSMUSP00000019907

PTM databases

iPTMnetiQ7TSG3
PhosphoSitePlusiQ7TSG3

Proteomic databases

EPDiQ7TSG3
MaxQBiQ7TSG3
PaxDbiQ7TSG3
PeptideAtlasiQ7TSG3
PRIDEiQ7TSG3

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019907; ENSMUSP00000019907; ENSMUSG00000019773
GeneIDi67141
KEGGimmu:67141
UCSCiuc007egj.1 mouse

Organism-specific databases

CTDi26271
MGIiMGI:1914391 Fbxo5

Phylogenomic databases

eggNOGiENOG410IJ4T Eukaryota
ENOG4111MJS LUCA
GeneTreeiENSGT00530000063692
HOGENOMiHOG000035122
HOVERGENiHBG010089
InParanoidiQ7TSG3
KOiK10292
OMAiDYCTRCL
OrthoDBiEOG091G08DI
PhylomeDBiQ7TSG3
TreeFamiTF101170

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-MMU-174113 SCF-beta-TrCP mediated degradation of Emi1
R-MMU-176408 Regulation of APC/C activators between G1/S and early anaphase
R-MMU-176417 Phosphorylation of Emi1
R-MMU-68881 Mitotic Metaphase/Anaphase Transition

Miscellaneous databases

PROiPR:Q7TSG3
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019773 Expressed in 204 organ(s), highest expression level in dorsal pancreas
CleanExiMM_FBXO5
GenevisibleiQ7TSG3 MM

Family and domain databases

InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
PfamiView protein in Pfam
PF00646 F-box, 1 hit
SUPFAMiSSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS51872 ZF_ZBR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFBX5_MOUSE
AccessioniPrimary (citable) accession number: Q7TSG3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 1, 2003
Last modified: November 7, 2018
This is version 117 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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