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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

Pathway: 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 transferase activity Source: UniProtKB

GO - Biological processi

  • positive regulation of protein ubiquitination Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • telomere maintenance Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_16907. Association of TriC/CCT with target proteins during biosynthesis.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
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
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:13583. FBXO4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • SCF ubiquitin ligase complex Source: UniProtKB
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi12 – 121S → A: Reduces homodimerization. Reduces ubiquitination of CCND1.
Mutagenesisi12 – 121S → E: No effect on homodimerization.
Mutagenesisi13 – 131P → A: Reduces homodimerization.
Mutagenesisi23 – 231L → A: Abolishes homodimerization.
Mutagenesisi341 – 3411C → W: Abolishes interaction with TERF1. 1 Publication
Mutagenesisi345 – 3451A → R: Abolishes interaction with TERF1. 1 Publication

Organism-specific databases

PharmGKBiPA28044.

Polymorphism and mutation databases

BioMutaiFBXO4.
DMDMi60416426.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 387387F-box only protein 4PRO_0000119879Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei12 – 121Phosphoserine3 Publications

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

MaxQBiQ9UKT5.
PaxDbiQ9UKT5.
PRIDEiQ9UKT5.

PTM databases

PhosphoSiteiQ9UKT5.

Expressioni

Gene expression databases

BgeeiQ9UKT5.
CleanExiHS_FBXO4.
ExpressionAtlasiQ9UKT5. baseline and differential.
GenevisibleiQ9UKT5. HS.

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
TERF1P542742EBI-960421,EBI-710997
TERF1P54274-23EBI-960421,EBI-711018
YWHAEP622585EBI-960409,EBI-356498
YwhaeP622602EBI-960409,EBI-356462From a different organism.

Protein-protein interaction databases

BioGridi117656. 17 interactions.
IntActiQ9UKT5. 7 interactions.
MINTiMINT-108507.
STRINGi9606.ENSP00000281623.

Structurei

Secondary structure

1
387
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi58 – 614Combined sources
Helixi64 – 729Combined sources
Helixi76 – 838Combined sources
Helixi87 – 937Combined sources
Helixi96 – 1049Combined sources
Helixi107 – 1093Combined sources
Helixi115 – 1173Combined sources
Helixi122 – 1254Combined sources
Helixi139 – 1468Combined sources
Beta strandi167 – 1693Combined sources
Beta strandi178 – 1825Combined sources
Helixi184 – 1863Combined sources
Beta strandi188 – 1914Combined sources
Helixi193 – 1986Combined sources
Helixi201 – 2033Combined sources
Helixi210 – 2123Combined sources
Beta strandi215 – 2173Combined sources
Beta strandi221 – 2288Combined sources
Beta strandi230 – 2356Combined sources
Helixi279 – 2857Combined sources
Beta strandi287 – 2948Combined sources
Helixi303 – 31311Combined sources
Helixi316 – 3194Combined sources
Beta strandi325 – 3339Combined sources
Helixi341 – 3477Combined sources
Helixi350 – 3534Combined sources
Beta strandi357 – 3637Combined sources
Turni364 – 3663Combined sources
Helixi370 – 3778Combined sources
Turni378 – 3836Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3L2OX-ray2.80B55-387[»]
3L82X-ray2.40B162-387[»]
ProteinModelPortaliQ9UKT5.
SMRiQ9UKT5. Positions 55-383.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKT5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini56 – 10247F-boxPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG39270.
GeneTreeiENSGT00390000014416.
HOGENOMiHOG000112550.
HOVERGENiHBG051585.
InParanoidiQ9UKT5.
KOiK10291.
OMAiHEWQDEF.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti41 – 411E → D in AAF04468 (PubMed:10531035).Curated
Sequence conflicti95 – 951D → N in AAF04468 (PubMed:10531035).Curated
Sequence conflicti120 – 1223DLE → YLQ in AAF04468 (PubMed:10531035).Curated
Sequence conflicti132 – 1321T → S in AAF04468 (PubMed:10531035).Curated
Sequence conflicti144 – 1441R → L in AAF04468 (PubMed:10531035).Curated
Sequence conflicti174 – 1741Q → P in AAF04468 (PubMed:10531035).Curated
Sequence conflicti181 – 1811M → L in AAF04468 (PubMed:10531035).Curated
Sequence conflicti185 – 1851G → R in AAF04468 (PubMed:10531035).Curated
Sequence conflicti188 – 1881E → Q in AAF04468 (PubMed:10531035).Curated
Sequence conflicti198 – 1981M → L in AAF04468 (PubMed:10531035).Curated
Sequence conflicti268 – 2692QQ → RP in AAF04468 (PubMed:10531035).Curated
Sequence conflicti282 – 2821V → L in AAF04468 (PubMed:10531035).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti8 – 81S → R in esophagus cancer samples. 1 Publication
Corresponds to variant rs2231917 [ dbSNP | Ensembl ].
VAR_063500
Natural varianti12 – 121S → L in esophagus cancer sample; impairs homodimerization and reduces ubiquitin ligase activity. 1 Publication
VAR_063501
Natural varianti13 – 131P → S in esophagus cancer sample. 1 Publication
VAR_063502
Natural varianti23 – 231L → Q in esophagus cancer samples. 1 Publication
VAR_063503
Natural varianti76 – 761P → T in esophagus cancer samples; impairs interaction with SKP1. 1 Publication
VAR_063504

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei300 – 3078RHEWQDEF → SKYSYVHF in isoform 2. 1 PublicationVSP_012977
Alternative sequencei308 – 38780Missing in isoform 2. 1 PublicationVSP_012978Add
BLAST

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.3. human. [Q9UKT5-2]
uc003jmq.3. 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
EntryMethodResolution (Å)ChainPositionsPDBsum
3L2OX-ray2.80B55-387[»]
3L82X-ray2.40B162-387[»]
ProteinModelPortaliQ9UKT5.
SMRiQ9UKT5. Positions 55-383.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117656. 17 interactions.
IntActiQ9UKT5. 7 interactions.
MINTiMINT-108507.
STRINGi9606.ENSP00000281623.

PTM databases

PhosphoSiteiQ9UKT5.

Polymorphism and mutation databases

BioMutaiFBXO4.
DMDMi60416426.

Proteomic databases

MaxQBiQ9UKT5.
PaxDbiQ9UKT5.
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.3. human. [Q9UKT5-2]
uc003jmq.3. human. [Q9UKT5-1]

Organism-specific databases

CTDi26272.
GeneCardsiGC05P041925.
HGNCiHGNC:13583. FBXO4.
MIMi609090. gene.
neXtProtiNX_Q9UKT5.
PharmGKBiPA28044.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG39270.
GeneTreeiENSGT00390000014416.
HOGENOMiHOG000112550.
HOVERGENiHBG051585.
InParanoidiQ9UKT5.
KOiK10291.
OMAiHEWQDEF.
PhylomeDBiQ9UKT5.
TreeFamiTF331105.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_16907. Association of TriC/CCT with target proteins during biosynthesis.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiFBXO4. human.
EvolutionaryTraceiQ9UKT5.
GeneWikiiFBXO4.
GenomeRNAii26272.
NextBioi48565.
PROiQ9UKT5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UKT5.
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...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH SKP1 AND CUL1.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-387.
    Tissue: Fetal brain.
  5. "The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance."
    Lee T.H., Perrem K., Harper J.W., Lu K.P., Zhou X.Z.
    J. Biol. Chem. 281:759-768(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TERF1, FUNCTION IN UBIQUITINATION OF TERF1.
  6. "Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer."
    Barbash O., Zamfirova P., Lin D.I., Chen X., Yang K., Nakagawa H., Lu F., Rustgi A.K., Diehl J.A.
    Cancer Cell 14:68-78(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, INTERACTION WITH SKP1, PHOSPHORYLATION AT SER-12, VARIANTS ARG-8; LEU-12; SER-13; GLN-23 AND THR-76, CHARACTERIZATION OF VARIANTS LEU-12; SER-13 AND GLN-23.
  7. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  8. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  9. "Structural basis of selective ubiquitination of TRF1 by SCFFbx4."
    Zeng Z., Wang W., Yang Y., Chen Y., Yang X., Diehl J.A., Liu X., Lei M.
    Dev. Cell 18:214-225(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 162-387 IN COMPLEX WITH TERF1, FUNCTION, MUTAGENESIS OF CYS-341 AND ALA-345, SUBUNIT.
  10. "Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase."
    Li Y., Hao B.
    J. Biol. Chem. 285:13896-13906(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 55-387 IN COMPLEX WITH SKP1, FUNCTION, SUBUNIT.

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: June 24, 2015
This is version 124 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

External Data

Dasty 3

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 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.