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Protein

F-box only protein 4

Gene

FBXO4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiQ9UKT5
UniPathwayi
UPA00143

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

EuPathDBiHostDB:ENSG00000151876.12
HGNCiHGNC:13583 FBXO4
MIMi609090 gene
neXtProtiNX_Q9UKT5

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

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
ProteomicsDBi84849
84850 [Q9UKT5-2]

PTM databases

iPTMnetiQ9UKT5
PhosphoSitePlusiQ9UKT5

Expressioni

Gene expression databases

BgeeiENSG00000151876 Expressed in 161 organ(s), highest expression level in body of pancreas
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi117656, 24 interactors
IntActiQ9UKT5, 8 interactors
MINTiQ9UKT5
STRINGi9606.ENSP00000281623

Structurei

Secondary structure

1387
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UKT5
SMRiQ9UKT5
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKT5

Family & Domainsi

Domains and Repeats

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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR039588 FBXO4
PANTHERiPTHR16008 PTHR16008, 1 hit
PfamiView protein in Pfam
PF00646 F-box, 1 hit
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SUPFAMiSSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RAJ6D6RAJ6_HUMAN
F-box only protein 4
FBXO4
305Annotation score:
D6REP2D6REP2_HUMAN
F-box only protein 4
FBXO4
154Annotation score:
D6RAU6D6RAU6_HUMAN
F-box only protein 4
FBXO4
64Annotation score:

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 dbSNP:rs2231917Ensembl.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

Similar proteinsi

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, 24 interactors
IntActiQ9UKT5, 8 interactors
MINTiQ9UKT5
STRINGi9606.ENSP00000281623

PTM databases

iPTMnetiQ9UKT5
PhosphoSitePlusiQ9UKT5

Polymorphism and mutation databases

BioMutaiFBXO4
DMDMi60416426

Proteomic databases

PaxDbiQ9UKT5
PeptideAtlasiQ9UKT5
PRIDEiQ9UKT5
ProteomicsDBi84849
84850 [Q9UKT5-2]

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
EuPathDBiHostDB:ENSG00000151876.12
GeneCardsiFBXO4
HGNCiHGNC:13583 FBXO4
HPAiHPA003362
MIMi609090 gene
neXtProtiNX_Q9UKT5
OpenTargetsiENSG00000151876
PharmGKBiPA28044
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-8951664 Neddylation
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiQ9UKT5

Miscellaneous databases

ChiTaRSiFBXO4 human
EvolutionaryTraceiQ9UKT5
GeneWikiiFBXO4
GenomeRNAii26272
PROiPR:Q9UKT5
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151876 Expressed in 161 organ(s), highest expression level in body of pancreas
CleanExiHS_FBXO4
ExpressionAtlasiQ9UKT5 baseline and differential
GenevisibleiQ9UKT5 HS

Family and domain databases

InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR039588 FBXO4
PANTHERiPTHR16008 PTHR16008, 1 hit
PfamiView protein in Pfam
PF00646 F-box, 1 hit
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SUPFAMiSSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFBX4_HUMAN
AccessioniPrimary (citable) accession number: Q9UKT5
Secondary accession number(s): Q68CU8, Q86VT8, Q9UK98
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: March 1, 2005
Last modified: November 7, 2018
This is version 154 of the entry and version 2 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 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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