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Protein

F-box only protein 5

Gene

FBXO5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Regulator of APC activity during mitotic and meiotic cell cycle (PubMed:17485488, PubMed:17234884, PubMed:17875940, PubMed:23708001, PubMed:23708605, PubMed:16921029). During mitotic cell cycle plays a role as both substrate and inhibitor of APC-FZR1 complex (PubMed:29875408, PubMed:17485488, PubMed:17234884, PubMed:17875940, PubMed:23708001, PubMed:23708605, PubMed:16921029). During G1 phase, plays a role as substrate of APC-FZR1 complex E3 ligase (PubMed:29875408). Then switches as an inhibitor of APC-FZR1 complex during S and G2 leading to cell-cycle commitment (PubMed:29875408). 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 coreceptor, formed by FZR1 and ANAPC10; by suppressing ubiquitin ligation and chain elongation by APC by preventing the UBE2C and UBE2S activities (PubMed:23708605, PubMed:23708001, PubMed:16921029). 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 (PubMed:17234884, PubMed:17485488, PubMed:17875940). 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 (By similarity). Controls entry into the first meiotic division through inactivation of APC-FZR1 complex (By similarity). Promotes migration and osteogenic differentiation of mesenchymal stem cells (PubMed:29850565).By similarity8 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 fingeri374 – 422ZBR-typePROSITE-ProRule annotationAdd BLAST49

GO - Molecular functioni

  • anaphase-promoting complex binding Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein kinase binding Source: UniProtKB
  • ubiquitin ligase inhibitor activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176417 Phosphorylation of Emi1
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-68881 Mitotic Metaphase/Anaphase Transition
SIGNORiQ9UKT4
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
F-box only protein 5Curated
Alternative name(s):
Early mitotic inhibitor 11 Publication
Gene namesi
Name:FBXO5Imported
Synonyms:EMI11 Publication, FBX5Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112029.9
HGNCiHGNC:13584 FBXO5
MIMi606013 gene
neXtProtiNX_Q9UKT4

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi143E → A: Delays degradation. 1 Publication1
Mutagenesisi144D → A: Does not affect protein stability. 1 Publication1
Mutagenesisi145S → A: Does not affect protein stability; when associated with A-149. 1 Publication1
Mutagenesisi145S → E: Degraded in similar manner to wild-type. 3 Publications1
Mutagenesisi145S → N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-149. 3 Publications1
Mutagenesisi146G → V: Does not affect protein stability. 1 Publication1
Mutagenesisi148S → A: Degraded in similar manner to wild-type. 1 Publication1
Mutagenesisi149S → A: Does not affect protein stability; when associated with A-145. 1 Publication1
Mutagenesisi149S → E: Degraded in similar manner to wild-type. 3 Publications1
Mutagenesisi149S → N: Not mitotically degraded. Shows impaired interaction with BTRC and reduced phosphate incorporation; when associated with N-145. 3 Publications1
Mutagenesisi182S → A: Shows impaired interaction with BTRC. 1 Publication1
Mutagenesisi210 – 216KRNPKVD → AAAAAAA: Loss of interaction with EVI5. 1 Publication7
Mutagenesisi322 – 325RTPL → ATPA: Does not affect inhibition of UBE2S-catalyzed chain elongation. Efficiently inhibits the degradation of PTTG1 at relatively high concentration. Reduces the competitive ability of FBXO5 to inhibit the association of PTTG1 to APC. Can not compete with the APC substrate for APC binding. Decreases inhibition of CCNB1 ubiquitination by UBE2C. 2 Publications4
Mutagenesisi339 – 345Missing : Impairs CCNB1 ubiquitination by UBE2C; when associated with 356-Y--R-358 del. 1 Publication7
Mutagenesisi345L → A: Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with 346-S--T-355 del. 1 Publication1
Mutagenesisi346 – 355Missing : Inhibits CCNB1 ubiquitination by UBE2C. Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with A-345; A-356 and A-358. 1 Publication10
Mutagenesisi356 – 358Missing : Impairs CCNB1 ubiquitination by UBE2C; when associated with 339-K--L-345 del. 1 Publication3
Mutagenesisi356Y → A: Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with 346-S--T-355 del. 1 Publication1
Mutagenesisi358R → A: Substantially impairs inhibition of CCNB1 ubiquitination by UBE2C; when associated with 346-S--T-355 del. 1 Publication1
Mutagenesisi375L → A: Decreases UBE2C-mediated ubiquitination. 1 Publication1
Mutagenesisi376K → A: Decreases UBE2C-mediated ubiquitination. 1 Publication1
Mutagenesisi393R → A: Decreases UBE2C-mediated ubiquitination. 1 Publication1
Mutagenesisi401C → S: Reduced inhibition of APC. Does not affect the FBXO5-mediated inhibitory activity against ubiquitin chain assembly. Does not affect the FBXO5-mediated inhibitory activity against ubiquitin chain assembly; when associated with S-401. Does not affect inhibition of UBE2S-catalyzed chain elongation. Reduces the competitive ability of FBXO5 to inhibit the association of securin to APC. Can still compete with the APC substrate for APC binding. Fails to inhibit ubiquitin chain assembly by UBE2C or mono-ubiquitination by UBE2D1. Largely abolishes the inhibitory activity against protein degradation. Fails to inactivate APC-FZR1 complex. Allows FBXO5 degradation in the absence of CDK4 inhibitor. 3 Publications1
Mutagenesisi406C → S: Does not affect the inhibitory activity against chain assembly; when associated with S-401. 1 Publication1
Mutagenesisi409C → A: Decreases UBE2C-mediated ubiquitination. 1 Publication1
Mutagenesisi444 – 445LR → AA: Loses inhibitory activity on UBE2S-catalyzed chain elongation. 1 Publication2

Organism-specific databases

DisGeNETi26271
OpenTargetsiENSG00000112029
PharmGKBiPA28045

Polymorphism and mutation databases

BioMutaiFBXO5
DMDMi24636847

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001198811 – 447F-box only protein 5Add BLAST447

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei94PhosphoserineBy similarity1
Modified residuei102PhosphoserineCombined 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 (PubMed:12791267, PubMed:15469984). Phosphorylated by RPS6KA2; increases and stabilizes interaction with CDC20 (By similarity).By similarity2 Publications
Ubiquitinated by the SCF(BTRC) complex following phosphorylation by PLK1 (PubMed:15469984). Undergoes both 'Lys-11' and 'Lys-48'-linked polyubiquitination by APC-FZR1 complex leading to degradation by proteasome during G1 phase (PubMed:29875408). 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 (By similarity).By similarity2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UKT4
PaxDbiQ9UKT4
PeptideAtlasiQ9UKT4
PRIDEiQ9UKT4
ProteomicsDBi84847
84848 [Q9UKT4-2]

PTM databases

iPTMnetiQ9UKT4
PhosphoSitePlusiQ9UKT4

Expressioni

Developmental stagei

Accumulates in late G1 phase, levels rise during S phase and drop in early mitosis.1 Publication

Inductioni

Up-regulated at 7 days after osteogenic induction (PubMed:29850565). Down-regulated in late G2 phase or mitosis (PubMed:17485488). Down-regulated in G2 phase after DNA damage in a CDKN1A-dependent manner (PubMed:19211842). Down-regulated in G1 phase when APC-FZR1 complex is active and accumulates at the G1-S transition, coincident with the inactivation of APC-FZR1 complex (PubMed:29875408). At the G1-S transition, transcriptionally induced by the E2F transcription factor (PubMed:11988738).5 Publications

Gene expression databases

BgeeiENSG00000112029 Expressed in 170 organ(s), highest expression level in liver
CleanExiHS_FBXO5
GenevisibleiQ9UKT4 HS

Organism-specific databases

HPAiCAB008106
HPA029048

Interactioni

Subunit structurei

Part of a SCF (SKP1-cullin-F-box) protein ligase complex (By similarity). Interacts with BTRC; mediates proteolysis by the SCF ubiquitin ligase complex leading to activation of APC in late mitosis and subsequent mitotic progression (PubMed:12791267). Interacts with FZR1/CDH1 and the N-terminal substrate-binding domain of CDC20; prevents APC activation (PubMed:11988738). Also interacts with EVI5 which blocks its phosphorylation by PLK1 and prevents its subsequent binding to BTRC and degradation (PubMed:16439210). Interacts simultaneously with anaphase promoting complex (APC), through at least ANAPC2, CDC23, CDC27, the APC substrate GMNN and the APC activator FZR1 (PubMed:23708001, PubMed:26083744). 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 (PubMed:23708001). Interacts with RPS6KA2; cooperates to induce the metaphase arrest of early blastomeres; increases and stabilizes interaction of FBXO5 with CDC20 (By similarity).By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117655, 38 interactors
DIPiDIP-38023N
ELMiQ9UKT4
IntActiQ9UKT4, 22 interactors
MINTiQ9UKT4
STRINGi9606.ENSP00000229758

Structurei

Secondary structure

1447
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UKT4
SMRiQ9UKT4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini250 – 296F-boxAdd BLAST47

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni135 – 244Interaction with EVI51 PublicationAdd BLAST110
Regioni261 – 409Requires for efficient binding to CDC20By similarityAdd BLAST149
Regioni261 – 339Sufficient for interaction with RPS6KA2; Prevents association of CDC20 with RPS6KA2By similarityAdd BLAST79
Regioni305 – 447Inhibits APC ubiquitin ligase activity1 PublicationAdd BLAST143
Regioni322 – 325Competitively blocks access of APC substrates to the D-box coreceptor formed by FZR1 and ANAPC101 Publication4
Regioni378 – 420Allows a rapid multiple mono-ubiquitination of the APC substrate, but strongly inhibits the slow ubiquitin chain elongation catalyzed by UBCH101 PublicationAdd BLAST43
Regioni437 – 447Sufficient 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 UBE2D11 PublicationAdd BLAST11

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri374 – 422ZBR-typePROSITE-ProRule annotationAdd BLAST49

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJ4T Eukaryota
ENOG4111MJS LUCA
GeneTreeiENSGT00530000063692
HOGENOMiHOG000035122
HOVERGENiHBG010089
InParanoidiQ9UKT4
KOiK10292
OMAiDYCTRCL
OrthoDBiEOG091G08DI
PhylomeDBiQ9UKT4
TreeFamiTF101170

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9UKT4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSRRPCSCAL RPPRCSCSAS PSAVTAAGRP RPSDSCKEES STLSVKMKCD
60 70 80 90 100
FNCNHVHSGL KLVKPDDIGR LVSYTPAYLE GSCKDCIKDY ERLSCIGSPI
110 120 130 140 150
VSPRIVQLET ESKRLHNKEN QHVQQTLNST NEIEALETSR LYEDSGYSSF
160 170 180 190 200
SLQSGLSEHE EGSLLEENFG DSLQSCLLQI QSPDQYPNKN LLPVLHFEKV
210 220 230 240 250
VCSTLKKNAK RNPKVDREML KEIIARGNFR LQNIIGRKMG LECVDILSEL
260 270 280 290 300
FRRGLRHVLA TILAQLSDMD LINVSKVSTT WKKILEDDKG AFQLYSKAIQ
310 320 330 340 350
RVTENNNKFS PHASTREYVM FRTPLASVQK SAAQTSLKKD AQTKLSNQGD
360 370 380 390 400
QKGSTYSRHN EFSEVAKTLK KNESLKACIR CNSPAKYDCY LQRATCKREG
410 420 430 440
CGFDYCTKCL CNYHTTKDCS DGKLLKASCK IGPLPGTKKS KKNLRRL
Length:447
Mass (Da):50,146
Last modified:May 1, 2000 - v1
Checksum:i196FBC2578F92120
GO
Isoform 2 (identifier: Q9UKT4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-46: Missing.

Show »
Length:401
Mass (Da):45,353
Checksum:i8E9E775625E62A4F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti212N → D in BAG51487 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024440107Q → E2 PublicationsCorresponds to variant dbSNP:rs2073260Ensembl.1
Natural variantiVAR_049038164L → F. Corresponds to variant dbSNP:rs7763565Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0413621 – 46Missing in isoform 2. 1 PublicationAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129535 mRNA Translation: AAF04469.1
AY079515 mRNA Translation: AAL86610.1
AK055221 mRNA Translation: BAG51487.1
AL080276 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW47719.1
BC018905 mRNA Translation: AAH18905.1
CCDSiCCDS47501.1 [Q9UKT4-2]
CCDS5242.1 [Q9UKT4-1]
RefSeqiNP_001135994.1, NM_001142522.2 [Q9UKT4-2]
NP_036309.1, NM_012177.4 [Q9UKT4-1]
UniGeneiHs.520506
Hs.713801

Genome annotation databases

EnsembliENST00000229758; ENSP00000229758; ENSG00000112029 [Q9UKT4-1]
ENST00000367241; ENSP00000356210; ENSG00000112029 [Q9UKT4-2]
GeneIDi26271
KEGGihsa:26271
UCSCiuc003qpg.4 human [Q9UKT4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129535 mRNA Translation: AAF04469.1
AY079515 mRNA Translation: AAL86610.1
AK055221 mRNA Translation: BAG51487.1
AL080276 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW47719.1
BC018905 mRNA Translation: AAH18905.1
CCDSiCCDS47501.1 [Q9UKT4-2]
CCDS5242.1 [Q9UKT4-1]
RefSeqiNP_001135994.1, NM_001142522.2 [Q9UKT4-2]
NP_036309.1, NM_012177.4 [Q9UKT4-1]
UniGeneiHs.520506
Hs.713801

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2M6NNMR-A364-447[»]
4UI9electron microscopy3.60S1-447[»]
U1-27[»]
ProteinModelPortaliQ9UKT4
SMRiQ9UKT4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117655, 38 interactors
DIPiDIP-38023N
ELMiQ9UKT4
IntActiQ9UKT4, 22 interactors
MINTiQ9UKT4
STRINGi9606.ENSP00000229758

PTM databases

iPTMnetiQ9UKT4
PhosphoSitePlusiQ9UKT4

Polymorphism and mutation databases

BioMutaiFBXO5
DMDMi24636847

Proteomic databases

EPDiQ9UKT4
PaxDbiQ9UKT4
PeptideAtlasiQ9UKT4
PRIDEiQ9UKT4
ProteomicsDBi84847
84848 [Q9UKT4-2]

Protocols and materials databases

DNASUi26271
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229758; ENSP00000229758; ENSG00000112029 [Q9UKT4-1]
ENST00000367241; ENSP00000356210; ENSG00000112029 [Q9UKT4-2]
GeneIDi26271
KEGGihsa:26271
UCSCiuc003qpg.4 human [Q9UKT4-1]

Organism-specific databases

CTDi26271
DisGeNETi26271
EuPathDBiHostDB:ENSG00000112029.9
GeneCardsiFBXO5
HGNCiHGNC:13584 FBXO5
HPAiCAB008106
HPA029048
MIMi606013 gene
neXtProtiNX_Q9UKT4
OpenTargetsiENSG00000112029
PharmGKBiPA28045
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJ4T Eukaryota
ENOG4111MJS LUCA
GeneTreeiENSGT00530000063692
HOGENOMiHOG000035122
HOVERGENiHBG010089
InParanoidiQ9UKT4
KOiK10292
OMAiDYCTRCL
OrthoDBiEOG091G08DI
PhylomeDBiQ9UKT4
TreeFamiTF101170

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176417 Phosphorylation of Emi1
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-68881 Mitotic Metaphase/Anaphase Transition
SIGNORiQ9UKT4

Miscellaneous databases

GeneWikiiFBXO5
GenomeRNAii26271
PROiPR:Q9UKT4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112029 Expressed in 170 organ(s), highest expression level in liver
CleanExiHS_FBXO5
GenevisibleiQ9UKT4 HS

Family and domain databases

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

Entry informationi

Entry nameiFBX5_HUMAN
AccessioniPrimary (citable) accession number: Q9UKT4
Secondary accession number(s): B3KNX5
, Q5TF47, Q8WV29, Q9UGC8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 2002
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 153 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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