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FBXO4 F-box protein 4 [ Homo sapiens (human) ]

Gene ID: 26272, updated on 11-Apr-2024

Summary

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Official Symbol
FBXO4provided by HGNC
Official Full Name
F-box protein 4provided by HGNC
Primary source
HGNC:HGNC:13583
See related
Ensembl:ENSG00000151876 MIM:609090; AllianceGenome:HGNC:13583
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FBX4
Summary
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]
Expression
Ubiquitous expression in thyroid (RPKM 3.2), lymph node (RPKM 2.5) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
5p13.1
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (41925281..42040404)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (42181685..42298494)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (41925383..41941845)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22508 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:41904130-41904676 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22510 Neighboring gene zinc finger protein 626 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15986 Neighboring gene Sharpr-MPRA regulatory region 10845 Neighboring gene ribosomal protein S2 pseudogene 22 Neighboring gene RAB7A interacting MON1-CCZ1 complex subunit 1 Neighboring gene MPRA-validated peak5238 silencer Neighboring gene ribosomal protein SA pseudogene 38 Neighboring gene methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase pseudogene 6 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:42078724-42079249 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:42090075-42091274 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85089 Neighboring gene long intergenic non-protein coding RNA 2996 Neighboring gene NANOG hESC enhancer GRCh37_chr5:42225166-42225693 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85146 Neighboring gene NANOG hESC enhancer GRCh37_chr5:42288621-42289193 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_85179 Neighboring gene GHR upstream promoter region module A Neighboring gene zinc finger protein 35 pseudogene Neighboring gene SERPINE1 mRNA binding protein 1 pseudogene 6 Neighboring gene growth hormone receptor

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer. Chu X, et al. Biochem Biophys Res Commun, 2014 Apr 25. PMID 24704453
  2. FBX4 mediates rapid cyclin D1 proteolysis upon DNA damage in immortalized esophageal epithelial cells. Liu J, et al. Biochem Biophys Res Commun, 2021 May 21. PMID 33784509
  3. Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Barbash O, et al. Cancer Cell, 2008 Jul 8. PMID 18598945, Free PMC Article
  4. Structural basis of selective ubiquitination of TRF1 by SCFFbx4. Zeng Z, et al. Dev Cell, 2010 Feb 16. PMID 20159592, Free PMC Article
  5. Heat shock factor 1 deficiency via its downstream target gene alphaB-crystallin (Hspb5) impairs p53 degradation. Jin X, et al. J Cell Biochem, 2009 Jun 1. PMID 19343786, Free PMC Article

See all (56) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. FBX4 mediates rapid cyclin D1 proteolysis upon DNA damage in immortalized esophageal epithelial cells.
    Title: FBX4 mediates rapid cyclin D1 proteolysis upon DNA damage in immortalized esophageal epithelial cells.
  2. in head and neck squamous cell carcinoma, fragile X mental retardation syndrome related protein 1 (Fxr1) overexpression correlates with reduced F-box protein 4 (Fbxo4) levels.
    Title: Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma.
  3. FBXO4 is the E3 ubiquitin ligase to interact with and promote Mcl-1 ubiquitination and degradation.
    Title: FBXO4 inhibits lung cancer cell survival by targeting Mcl-1 for degradation.
  4. results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant cyclin D1 expression in human cancers.
    Title: Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer.
  5. The FBXO4 I377M mutant exhibits impaired cyclin D1 recruitment and ubiquitylation.
    Title: The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma.
  6. 14-3-3varepsilon binds to Ser12-phosphorylated Fbx4 to mediate dimerization and function.
    Title: Phosphorylation-dependent regulation of SCF(Fbx4) dimerization and activity involves a novel component, 14-3-3ɛ.
  7. Biochemical studies indicate that both the N-terminal domain and a loop connecting the linker and C-terminal domain of Fbx4 are critical for the dimerization and activation of the protein.
    Title: Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase.
  8. results reveal an atypical small GTPase domain within Fbx4 as a substrate-binding motif for SCF(Fbx4) and uncover a mechanism for selective ubiquitination and degradation of TRF1 in telomere homeostasis control
    Title: Structural basis of selective ubiquitination of TRF1 by SCFFbx4.
  9. Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.
    Title: Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer.
  10. Fbx4 is a central regulator of Pin2/TRF1 protein abundance and alterations in the stability of Pin2/TRF1 can have a dramatic impact on telomere length
    Title: The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance.
Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ10141, DKFZp547N213

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase activity IEA
Inferred from Electronic Annotation
more info
  
enables ubiquitin-like ligase-substrate adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to ionizing radiation IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular senescence IEA
Inferred from Electronic Annotation
more info
  
involved_in common myeloid progenitor cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of fibroblast proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of protein localization to nucleus IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of protein polyubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of telomere maintenance via telomerase IC
Inferred by Curator
more info
 PubMed 
involved_in positive regulation of telomere maintenance via telomerase IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in post-transcriptional regulation of gene expression IEA
Inferred from Electronic Annotation
more info
  
involved_in protein destabilization IEA
Inferred from Electronic Annotation
more info
  
involved_in protein polyubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein polyubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein ubiquitination TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of DNA damage checkpoint IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein stability IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of protein stability IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of SCF ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
F-box only protein 4
Names
F-box protein Fbx4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001297437.2 → NP_001284366.1  F-box only protein 4 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an internal exon in the 3' coding region, which results in a translational frameshift, compared to variant 1. The resulting isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC034222
    Consensus CDS
    CCDS75238.1
    UniProtKB/TrEMBL
    D6RAJ6
    Related
    ENSP00000421749.1, ENST00000509134.1
    Conserved Domains (2) summary
    cd11656
    Location:162 → 299
    FBX4_GTPase_like; C-terminal GTPase-like domain of F-Box Only Protein 4
    pfam12937
    Location:59 → 105
    F-box-like; F-box-like

  2. NM_012176.3 → NP_036308.1  F-box only protein 4 isoform 1

    See identical proteins and their annotated locations for NP_036308.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    AC034222, AK024075, BC040011, BC048098
    Consensus CDS
    CCDS3938.1
    UniProtKB/Swiss-Prot
    Q68CU8, Q86VT8, Q9UK98, Q9UKT5
    UniProtKB/TrEMBL
    B3KNA0
    Related
    ENSP00000281623.3, ENST00000281623.8
    Conserved Domains (2) summary
    cd11656
    Location:162 → 384
    FBX4_GTPase_like; C-terminal GTPase-like domain of F-Box Only Protein 4
    pfam12937
    Location:59 → 100
    F-box-like; F-box-like

  3. NM_033484.3 → NP_277019.1  F-box only protein 4 isoform 2

    See identical proteins and their annotated locations for NP_277019.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks two exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC034222, AF176703, AU143782
    Consensus CDS
    CCDS3939.1
    UniProtKB/Swiss-Prot
    Q9UKT5
    Related
    ENSP00000296812.2, ENST00000296812.6
    Conserved Domains (2) summary
    cd11656
    Location:162 → 299
    FBX4_GTPase_like; C-terminal GTPase-like domain of F-Box Only Protein 4
    pfam12937
    Location:59 → 105
    F-box-like; F-box-like

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    41925281..42040404
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011514026.4 → XP_011512328.1  F-box only protein 4 isoform X1

    Conserved Domains (2) summary
    cd11656
    Location:162 → 305
    FBX4_GTPase_like; C-terminal GTPase-like domain of F-Box Only Protein 4
    pfam12937
    Location:59 → 105
    F-box-like; F-box-like

  2. XM_011514027.3 → XP_011512329.1  F-box only protein 4 isoform X2

    Conserved Domains (1) summary
    cd11656
    Location:28 → 250
    FBX4_GTPase_like; C-terminal GTPase-like domain of F-Box Only Protein 4

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    42181685..42298494
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352356.1 → XP_054208331.1  F-box only protein 4 isoform X1

  2. XM_054352357.1 → XP_054208332.1  F-box only protein 4 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UKT5.2 GenPept UniProtKB/Swiss-Prot:Q9UKT5

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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