FBXO4 Gene (Protein Coding)

F-Box Protein 4

GC05P041945
GIFtS:
38
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing... See more...

Aliases for FBXO4 Gene

Aliases for FBXO4 Gene

  • F-Box Protein 4 2 3 5
  • F-Box Only Protein 4 2 3 4
  • FBX4 2 3 4
  • F-Box Protein Fbx4 3
  • FBXO4 5

External Ids for FBXO4 Gene

Previous GeneCards Identifiers for FBXO4 Gene

  • GC05P042223
  • GC05P043025
  • GC05P041925
  • GC05P041970
  • GC05P041961
  • GC05P041878
  • GC05P041938

Summaries for FBXO4 Gene

Entrez Gene Summary for FBXO4 Gene

  • This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

GeneCards Summary for FBXO4 Gene

FBXO4 (F-Box Protein 4) is a Protein Coding gene. Diseases associated with FBXO4 include Adult Brain Stem Glioma. Among its related pathways are Ubiquitin mediated proteolysis and Innate Immune System. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot Summary for FBXO4 Gene

  • 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.

Gene Wiki entry for FBXO4 Gene

Additional gene information for FBXO4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FBXO4 Gene

Genomics for FBXO4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for FBXO4 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH05J041924 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 261.1 +7.3 7340 2.4 ZSCAN16 CHD2 TBP MNT DEK IKZF1 SMAD5 IRF2 ZFP64 MBD2 FBXO4 OXCT1 LOC100419715 HSALNG0041434 GHR
GH05J041903 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 73.9 -13.6 -13560 2.6 ZSCAN16 TBP ZBTB10 SP1 MXD4 NR2C1 DEK MNT IKZF1 SMAD5 C5orf51 HSALNG0041433 FBXO4 SERBP1P6 OXCT1-AS1 CCDC152
GH05J041869 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.8 -47.9 -47859 2.8 ZSCAN16 TBP MNT IKZF1 SMAD5 MBD2 POLR2A BRCA1 BHLHE40 ZIC2 OXCT1 ENSG00000286164 OXCT1-AS1 C5orf51 FBXO4 LOC102723752 PLCXD3
GH05J041747 Enhancer 0.8 Ensembl 15.4 -170.5 -170460 0.8 ZNF513 ZNF132 PRDM6 ZNF571 KLF16 ZNF624 INSM2 LCORL RCOR1 ZNF398 FBXO4 MK280073-522 RF00017-4598 OXCT1 PLCXD3
GH05J041856 Enhancer 0.8 FANTOM5 ENCODE 11 -61.2 -61217 0.2 DEK CTCF REST TRIM22 SMC3 RAD21 RFX5 ZEB2 SCRT1 ZNF143 FBXO4 C5orf51 LOC102723752 piR-61580-514 OXCT1 PLCXD3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FBXO4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for FBXO4

Top Transcription factor binding sites by QIAGEN in the FBXO4 gene promoter:
  • aMEF-2
  • AML1a
  • GATA-1
  • MEF-2A
  • Msx-1
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4

Genomic Locations for FBXO4 Gene

Latest Assembly
chr5:41,918,061-42,040,230
(GRCh38/hg38)
Size:
122,170 bases
Orientation:
Plus strand

Previous Assembly
chr5:41,925,383-41,941,845
(GRCh37/hg19 by Entrez Gene)
Size:
16,463 bases
Orientation:
Plus strand

chr5:41,925,356-41,941,845
(GRCh37/hg19 by Ensembl)
Size:
16,490 bases
Orientation:
Plus strand

Genomic View for FBXO4 Gene

Genes around FBXO4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FBXO4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FBXO4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for FBXO4 Gene

Proteins for FBXO4 Gene

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  • Protein details for FBXO4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UKT5-FBX4_HUMAN
    Recommended name:
    F-box only protein 4
    Protein Accession:
    Q9UKT5
    Secondary Accessions:
    • Q68CU8
    • Q86VT8
    • Q9UK98

    Protein attributes for FBXO4 Gene

    Size:
    387 amino acids
    Molecular mass:
    44136 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for FBXO4 Gene

    Alternative splice isoforms for FBXO4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FBXO4 Gene

Protein Expression for FBXO4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for FBXO4 Gene

  • 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.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FBXO4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for FBXO4 Gene

Domains & Families for FBXO4 Gene

Gene Families for FBXO4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for FBXO4 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FBXO4 Gene

GenScript: Design optimal peptide antigens:
  • F-box only protein 4 (FBX4_HUMAN)
genes like me logo Genes that share domains with FBXO4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for FBXO4 Gene

Function for FBXO4 Gene

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  6. Cell Lines for research

Molecular function for FBXO4 Gene

UniProtKB/Swiss-Prot Function:
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.

Phenotypes From GWAS Catalog for FBXO4 Gene

Gene Ontology (GO) - Molecular Function for FBXO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IDA 10531035
GO:0005515 protein binding IEA,IPI 16278047
GO:0042803 protein homodimerization activity IPI 20181953
GO:0061630 ubiquitin protein ligase activity IEA --
genes like me logo Genes that share ontologies with FBXO4: view
genes like me logo Genes that share phenotypes with FBXO4: view

Animal Models for FBXO4 Gene

MGI Knock Outs for FBXO4:

Animal Models for research

miRNA for FBXO4 Gene

miRTarBase miRNAs that target FBXO4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FBXO4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for FBXO4 Gene

Localization for FBXO4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FBXO4 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FBXO4 gene
Compartment Confidence
cytosol 4
nucleus 3
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FBXO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000151 ubiquitin ligase complex IDA 10531035
GO:0005737 cytoplasm IDA 21378169
GO:0005829 cytosol TAS --
GO:0019005 SCF ubiquitin ligase complex IEA,IDA 20181953
genes like me logo Genes that share ontologies with FBXO4: view

Pathways & Interactions for FBXO4 Gene

genes like me logo Genes that share pathways with FBXO4: view

UniProtKB/Swiss-Prot Q9UKT5-FBX4_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for FBXO4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for FBXO4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IDA,TAS --
GO:0000723 telomere maintenance IMP --
GO:0006511 ubiquitin-dependent protein catabolic process IDA --
GO:0007568 aging IEA --
GO:0010608 posttranscriptional regulation of gene expression IEA --
genes like me logo Genes that share ontologies with FBXO4: view

Drugs & Compounds for FBXO4 Gene

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No Compound Related Data Available

Transcripts for FBXO4 Gene

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mRNA/cDNA for FBXO4 Gene

3 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FBXO4

Alternative Splicing Database (ASD) splice patterns (SP) for FBXO4 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c · 6d ^ 7 ^ 8 ^ 9
SP1: - - - -
SP2: - -
SP3: - - -
SP4:
SP5: -
SP6: - -

Relevant External Links for FBXO4 Gene

GeneLoc Exon Structure for
FBXO4

Expression for FBXO4 Gene

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  1. Primer products for research
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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for FBXO4 Gene

mRNA expression in normal human tissues for FBXO4 Gene
mRNA expression by GTEx for FBXO4 GenemRNA expression by BioGPS for FBXO4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for FBXO4 Gene

This gene is overexpressed in Stomach (11.6), CD8 Tcells (9.9), Testis (9.6), and Ovary (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FBXO4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for FBXO4

SOURCE GeneReport for Unigene cluster for FBXO4 Gene:

Hs.165575

Evidence on tissue expression from TISSUES for FBXO4 Gene

  • Liver(4.3)
  • Nervous system(4.3)
genes like me logo Genes that share expression patterns with FBXO4: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for FBXO4 Gene

Orthologs for FBXO4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for FBXO4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia FBXO4 30 31
  • 98.89 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia FBXO4 30 31
  • 91.3 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia FBXO4 30 31
  • 90.61 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Fbxo4 30
  • 86.06 (n)
Mouse
(Mus musculus)
 Mammalia Fbxo4 30 17 31
  • 85.89 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia FBXO4 31
  • 73 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia FBXO4 31
  • 72 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves FBXO4 30 31
  • 67.57 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia FBXO4 31
  • 50 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia fbxo4 30
  • 61.4 (n)
Str.20453 30
African clawed frog
(Xenopus laevis)
 Amphibia Xl.24187 30
Zebrafish
(Danio rerio)
 Actinopterygii si:dkey-46a10.2 30
  • 55.52 (n)
FBXO4 31
  • 43 (a)
 OneToOne
Species where no ortholog for FBXO4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for FBXO4 Gene

ENSEMBL:
Gene Tree for FBXO4 (if available)
TreeFam:
Gene Tree for FBXO4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FBXO4: view image

Paralogs for FBXO4 Gene

No data available for Paralogs for FBXO4 Gene

Variants for FBXO4 Gene

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  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for FBXO4 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
rs2231917 Esophagus cancer samples p.Ser8Arg
VAR_063501 Esophagus cancer sample p.Ser12Leu
VAR_063502 Esophagus cancer sample p.Pro13Ser
VAR_063503 Esophagus cancer samples p.Leu23Gln
VAR_063504 Esophagus cancer samples p.Pro76Thr

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for FBXO4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for FBXO4 Gene

Variant ID Type Subtype PubMed ID
dgv1096e214 CNV gain 21293372
esv2762518 CNV loss 21179565
esv3604851 CNV gain 21293372
nsv830272 CNV gain 17160897
nsv830273 CNV gain 17160897

Variation tolerance for FBXO4 Gene

Residual Variation Intolerance Score: 35% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.61; 45.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FBXO4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FBXO4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FBXO4 Gene

Disorders for FBXO4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for FBXO4 Gene - From: COP

Disorder Aliases PubMed IDs
adult brain stem glioma
  • adult brainstem neuroglial tumor
- elite association - COSMIC cancer census association via MalaCards
Search FBXO4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for FBXO4

Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with FBXO4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FBXO4 Gene

Publications for FBXO4 Gene

  1. Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. (PMID: 20181953) Li Y … Hao B (The Journal of biological chemistry 2010) 3 4 23
  2. Identification of a family of human F-box proteins. (PMID: 10531035) Cenciarelli C … Pagano M (Current biology : CB 1999) 2 3 4
  3. A family of mammalian F-box proteins. (PMID: 10531037) Winston JT … Harper JW (Current biology : CB 1999) 2 3 4
  4. Structural basis of selective ubiquitination of TRF1 by SCFFbx4. (PMID: 20159592) Zeng Z … Lei M (Developmental cell 2010) 3 4
  5. Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. (PMID: 18598945) Barbash O … Diehl JA (Cancer cell 2008) 3 4

ExternalLinks

View latest publications for FBXO4 gene in Mastermind

Products for FBXO4 Gene

Sources for FBXO4 Gene