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Protein

F-box only protein 4

Gene

FBXO4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation. Recognizes TERF1 and promotes its ubiquitination together with UBE2D1.5 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.

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase activity Source: Ensembl
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151876-MONOMER.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ9UKT5.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
F-box only protein 4
Gene namesi
Name:FBXO4
Synonyms:FBX4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:13583. FBXO4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ParkinsonsUK-UCL
  • cytosol Source: Reactome
  • SCF ubiquitin ligase complex Source: UniProtKB
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi12S → A: Reduces homodimerization. Reduces ubiquitination of CCND1. 1
Mutagenesisi12S → E: No effect on homodimerization. 1
Mutagenesisi13P → A: Reduces homodimerization. 1
Mutagenesisi23L → A: Abolishes homodimerization. 1
Mutagenesisi341C → W: Abolishes interaction with TERF1. 1 Publication1
Mutagenesisi345A → R: Abolishes interaction with TERF1. 1 Publication1

Organism-specific databases

DisGeNETi26272.
OpenTargetsiENSG00000151876.
PharmGKBiPA28044.

Polymorphism and mutation databases

BioMutaiFBXO4.
DMDMi60416426.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001198791 – 387F-box only protein 4Add BLAST387

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei12PhosphoserineCombined sources1 Publication1
Modified residuei48PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-12 varies during the cell cycle. It is low in resting cells and high in the S phase and the G2/M phase of the cell cycle. Phosphorylation is decreased during late G1 phase (By similarity). Phosphorylation at Ser-12 promotes homodimerization and is necessary for optimal ubiquitin ligase activity towards CCND1.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9UKT5.
PeptideAtlasiQ9UKT5.
PRIDEiQ9UKT5.

PTM databases

iPTMnetiQ9UKT5.
PhosphoSitePlusiQ9UKT5.

Expressioni

Gene expression databases

BgeeiENSG00000151876.
CleanExiHS_FBXO4.
ExpressionAtlasiQ9UKT5. baseline and differential.
GenevisibleiQ9UKT5. HS.

Organism-specific databases

HPAiHPA003362.

Interactioni

Subunit structurei

Homodimer. Directly interacts with SKP1 and CUL1. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO4) formed of CUL1, SKP1, RBX1 and FBXO4. Interacts with TERF1. This interaction is prevented in the presence of GNL3L. Identified in a complex with CRYAB and CCND1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CUL1Q136162EBI-960409,EBI-359390
SKP1P632085EBI-960409,EBI-307486
TERF1P542742EBI-960421,EBI-710997
TERF1P54274-23EBI-960421,EBI-711018
YWHAEP622585EBI-960409,EBI-356498
YwhaeP622602EBI-960409,EBI-356462From a different organism.

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi117656. 18 interactors.
IntActiQ9UKT5. 7 interactors.
MINTiMINT-108507.
STRINGi9606.ENSP00000281623.

Structurei

Secondary structure

1387
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi58 – 61Combined sources4
Helixi64 – 72Combined sources9
Helixi76 – 83Combined sources8
Helixi87 – 93Combined sources7
Helixi96 – 104Combined sources9
Helixi107 – 109Combined sources3
Helixi115 – 117Combined sources3
Helixi122 – 125Combined sources4
Helixi139 – 146Combined sources8
Beta strandi167 – 169Combined sources3
Beta strandi178 – 182Combined sources5
Helixi184 – 186Combined sources3
Beta strandi188 – 191Combined sources4
Helixi193 – 198Combined sources6
Helixi201 – 203Combined sources3
Helixi210 – 212Combined sources3
Beta strandi215 – 217Combined sources3
Beta strandi221 – 228Combined sources8
Beta strandi230 – 235Combined sources6
Helixi279 – 285Combined sources7
Beta strandi287 – 294Combined sources8
Helixi303 – 313Combined sources11
Helixi316 – 319Combined sources4
Beta strandi325 – 333Combined sources9
Helixi341 – 347Combined sources7
Helixi350 – 353Combined sources4
Beta strandi357 – 363Combined sources7
Turni364 – 366Combined sources3
Helixi370 – 377Combined sources8
Turni378 – 383Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L2OX-ray2.80B55-387[»]
3L82X-ray2.40B162-387[»]
ProteinModelPortaliQ9UKT5.
SMRiQ9UKT5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKT5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 102F-boxPROSITE-ProRule annotationAdd BLAST47

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IE1X. Eukaryota.
ENOG410ZQ31. LUCA.
GeneTreeiENSGT00390000014416.
HOGENOMiHOG000112550.
HOVERGENiHBG051585.
InParanoidiQ9UKT5.
KOiK10291.
OMAiHEWQDEF.
OrthoDBiEOG091G0ALJ.
PhylomeDBiQ9UKT5.
TreeFamiTF331105.

Family and domain databases

InterProiIPR001810. F-box_dom.
[Graphical view]
PfamiPF00646. F-box. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UKT5-1) [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
MAGSEPRSGT NSPPPPFSDW GRLEAAILSG WKTFWQSVSK ERVARTTSRE
60 70 80 90 100
EVDEAASTLT RLPIDVQLYI LSFLSPHDLC QLGSTNHYWN ETVRDPILWR
110 120 130 140 150
YFLLRDLPSW SSVDWKSLPD LEILKKPISE VTDGAFFDYM AVYRMCCPYT
160 170 180 190 200
RRASKSSRPM YGAVTSFLHS LIIQNEPRFA MFGPGLEELN TSLVLSLMSS
210 220 230 240 250
EELCPTAGLP QRQIDGIGSG VNFQLNNQHK FNILILYSTT RKERDRAREE
260 270 280 290 300
HTSAVNKMFS RHNEGDDQQG SRYSVIPQIQ KVCEVVDGFI YVANAEAHKR
310 320 330 340 350
HEWQDEFSHI MAMTDPAFGS SGRPLLVLSC ISQGDVKRMP CFYLAHELHL
360 370 380
NLLNHPWLVQ DTEAETLTGF LNGIEWILEE VESKRAR
Length:387
Mass (Da):44,136
Last modified:March 1, 2005 - v2
Checksum:iBD5E8DD14B9733E9
GO
Isoform 2 (identifier: Q9UKT5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     300-307: RHEWQDEF → SKYSYVHF
     308-387: Missing.

Note: No experimental confirmation available.
Show »
Length:307
Mass (Da):35,003
Checksum:i62C85CD92410CC33
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41E → D in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti95D → N in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti120 – 122DLE → YLQ in AAF04468 (PubMed:10531035).Curated3
Sequence conflicti132T → S in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti144R → L in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti174Q → P in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti181M → L in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti185G → R in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti188E → Q in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti198M → L in AAF04468 (PubMed:10531035).Curated1
Sequence conflicti268 – 269QQ → RP in AAF04468 (PubMed:10531035).Curated2
Sequence conflicti282V → L in AAF04468 (PubMed:10531035).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0635008S → R in esophagus cancer samples. 1 PublicationCorresponds to variant rs2231917dbSNPEnsembl.1
Natural variantiVAR_06350112S → L in esophagus cancer sample; impairs homodimerization and reduces ubiquitin ligase activity. 1 Publication1
Natural variantiVAR_06350213P → S in esophagus cancer sample. 1 Publication1
Natural variantiVAR_06350323L → Q in esophagus cancer samples. 1 Publication1
Natural variantiVAR_06350476P → T in esophagus cancer samples; impairs interaction with SKP1. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012977300 – 307RHEWQDEF → SKYSYVHF in isoform 2. 1 Publication8
Alternative sequenceiVSP_012978308 – 387Missing in isoform 2. 1 PublicationAdd BLAST80

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176703 mRNA. Translation: AAF03703.1.
BC048098 mRNA. Translation: AAH48098.1.
CR749719 mRNA. Translation: CAH18486.1.
AF129534 mRNA. Translation: AAF04468.1.
CCDSiCCDS3938.1. [Q9UKT5-1]
CCDS3939.1. [Q9UKT5-2]
RefSeqiNP_036308.1. NM_012176.2. [Q9UKT5-1]
NP_277019.1. NM_033484.2. [Q9UKT5-2]
UniGeneiHs.165575.

Genome annotation databases

EnsembliENST00000281623; ENSP00000281623; ENSG00000151876. [Q9UKT5-1]
ENST00000296812; ENSP00000296812; ENSG00000151876. [Q9UKT5-2]
GeneIDi26272.
KEGGihsa:26272.
UCSCiuc003jmp.4. human. [Q9UKT5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176703 mRNA. Translation: AAF03703.1.
BC048098 mRNA. Translation: AAH48098.1.
CR749719 mRNA. Translation: CAH18486.1.
AF129534 mRNA. Translation: AAF04468.1.
CCDSiCCDS3938.1. [Q9UKT5-1]
CCDS3939.1. [Q9UKT5-2]
RefSeqiNP_036308.1. NM_012176.2. [Q9UKT5-1]
NP_277019.1. NM_033484.2. [Q9UKT5-2]
UniGeneiHs.165575.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L2OX-ray2.80B55-387[»]
3L82X-ray2.40B162-387[»]
ProteinModelPortaliQ9UKT5.
SMRiQ9UKT5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117656. 18 interactors.
IntActiQ9UKT5. 7 interactors.
MINTiMINT-108507.
STRINGi9606.ENSP00000281623.

PTM databases

iPTMnetiQ9UKT5.
PhosphoSitePlusiQ9UKT5.

Polymorphism and mutation databases

BioMutaiFBXO4.
DMDMi60416426.

Proteomic databases

PaxDbiQ9UKT5.
PeptideAtlasiQ9UKT5.
PRIDEiQ9UKT5.

Protocols and materials databases

DNASUi26272.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281623; ENSP00000281623; ENSG00000151876. [Q9UKT5-1]
ENST00000296812; ENSP00000296812; ENSG00000151876. [Q9UKT5-2]
GeneIDi26272.
KEGGihsa:26272.
UCSCiuc003jmp.4. human. [Q9UKT5-1]

Organism-specific databases

CTDi26272.
DisGeNETi26272.
GeneCardsiFBXO4.
HGNCiHGNC:13583. FBXO4.
HPAiHPA003362.
MIMi609090. gene.
neXtProtiNX_Q9UKT5.
OpenTargetsiENSG00000151876.
PharmGKBiPA28044.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE1X. Eukaryota.
ENOG410ZQ31. LUCA.
GeneTreeiENSGT00390000014416.
HOGENOMiHOG000112550.
HOVERGENiHBG051585.
InParanoidiQ9UKT5.
KOiK10291.
OMAiHEWQDEF.
OrthoDBiEOG091G0ALJ.
PhylomeDBiQ9UKT5.
TreeFamiTF331105.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000151876-MONOMER.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
SIGNORiQ9UKT5.

Miscellaneous databases

ChiTaRSiFBXO4. human.
EvolutionaryTraceiQ9UKT5.
GeneWikiiFBXO4.
GenomeRNAii26272.
PROiQ9UKT5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151876.
CleanExiHS_FBXO4.
ExpressionAtlasiQ9UKT5. baseline and differential.
GenevisibleiQ9UKT5. HS.

Family and domain databases

InterProiIPR001810. F-box_dom.
[Graphical view]
PfamiPF00646. F-box. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFBX4_HUMAN
AccessioniPrimary (citable) accession number: Q9UKT5
Secondary accession number(s): Q68CU8, Q86VT8, Q9UK98
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: March 1, 2005
Last modified: November 30, 2016
This is version 138 of the entry and version 2 of the sequence. [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 chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.