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

Summary

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: mouse all
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Genomic context

Location:: 5p13.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (41925281..42040404)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (42181685..42298494)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (41925383..41941845)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

sY3084 (e-PCR)
- UniSTS:515126

SHGC-32040 (e-PCR)
- UniSTS:21076

L18426 (e-PCR)
- UniSTS:34648

D1S1425 (e-PCR)
- UniSTS:149621

D11S3114 (e-PCR)
- UniSTS:152207

FBXO4 (e-PCR)
- UniSTS:505770

RH46228 (e-PCR)
- UniSTS:75950

GDB:335751 (e-PCR)
- UniSTS:156601

G20839 (e-PCR)
- UniSTS:75710

A006I14 (e-PCR)
- UniSTS:75711

FBXO4_635 (e-PCR)
- UniSTS:277231

FBXO4_V33 (e-PCR)
- UniSTS:277231

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
involved_in telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay 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)

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
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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

41925281..42040404

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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