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    FBXO3 F-box protein 3 [ Homo sapiens (human) ]

    Gene ID: 26273, updated on 2-Nov-2024

    Summary

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    Official Symbol
    FBXO3provided by HGNC
    Official Full Name
    F-box protein 3provided by HGNC
    Primary source
    HGNC:HGNC:13582
    See related
    Ensembl:ENSG00000110429 MIM:609089; AllianceGenome:HGNC:13582
    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
    FBA; FBX3
    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. Alternative splicing of this gene generates 2 transcript variants diverging at the 3' end. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 11.3), kidney (RPKM 10.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FBXO3 in Genome Data Viewer
    Location:
    11p13
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (33740944..33774520, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (33877954..33911529, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (33762490..33796066, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene KIAA1549 like Neighboring gene uncharacterized LOC105376617 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:33676703-33677902 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4582 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr11:33711673-33712872 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3239 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3240 Neighboring gene chromosome 11 open reading frame 91 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4583 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4584 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3241 Neighboring gene CD59 molecule (CD59 blood group) Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4585 Neighboring gene Sharpr-MPRA regulatory region 12829 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:33795080-33795580 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3243 Neighboring gene FBXO3 divergent transcript Neighboring gene Spi-C transcription factor pseudogene 1

    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 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. The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis. Chandra D, et al. J Mol Cell Cardiol, 2019 Jan. PMID 30448480, Free PMC Article
    2. The SCF(FBXO46) ubiquitin ligase complex mediates degradation of the tumor suppressor FBXO31 and thereby prevents premature cellular senescence. Choppara S, et al. J Biol Chem, 2018 Oct 19. PMID 30171069, Free PMC Article
    3. Crystal structure and interaction studies of the human FBxo3 ApaG domain. Krzysiak TC, et al. FEBS J, 2016 Jun. PMID 27010866, Free PMC Article
    4. Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH. Kainulainen M, et al. J Virol, 2014 Mar. PMID 24403578, Free PMC Article
    5. F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Li D, et al. Biochem Biophys Res Commun, 2015 Mar 20. PMID 25721664

    See all (71) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.
      Title: FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.
    2. FBXO3 potentiates vascular inflammation and atherosclerosis that can be effectively mitigated by a small molecule inhibitor.
      Title: The SCFFBXO3 ubiquitin E3 ligase regulates inflammation in atherosclerosis.
    3. reveal that FBXO46 is a crucial proteasomal regulator of FBXO31 and thereby prevents senescence in normal growth conditions
      Title: The SCF(FBXO46) ubiquitin ligase complex mediates degradation of the tumor suppressor FBXO31 and thereby prevents premature cellular senescence.
    4. we report the X-ray structure of the human FBxo3 ApaG domain, residues 278-407, at 2.0 A resolution
      Title: Crystal structure and interaction studies of the human FBxo3 ApaG domain.
    5. AIRE, which is phosphorylated on two specific residues near its N terminus, then binds to the F-box protein 3 (FBXO3) E3 ubiquitin ligase. In turn, this SCF(FBXO3) (SKP1-CUL1-F box) complex ubiquitylates AIRE, increases its binding to the positive transcription elongation factor b (P-TEFb), and potentiates its transcriptional activity.
      Title: FBXO3 Protein Promotes Ubiquitylation and Transcriptional Activity of AIRE (Autoimmune Regulator).
    6. Fbxo3 promotes the proteasomal degradation of Smurf1. Fbxo3 promotes the poly-ubiquitination of Smurf1.
      Title: F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation.
    7. Virulence factor NSs of rift valley fever virus recruits the FBXO3 to degrade subunit p62 of general transcription factor TFIIH.
      Title: Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.
    8. controls TRAF adaptor stability to regulate inflammation
      Title: A combinatorial F box protein directed pathway controls TRAF adaptor stability to regulate inflammation.
    9. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    10. Fbx3 formed SCF(Fbx3) ubiquitin ligase and promoted the degradation of HIPK2 and p300 by the ubiquitin-proteasome pathway
      Title: PML activates transcription by protecting HIPK2 and p300 from SCFFbx3-mediated degradation.
    Submit: New GeneRIF Correction

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genetics of coronary artery calcification among African Americans, a meta-analysis.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat is identified to have a physical interaction with F-box protein 3 (FBXO3) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp564B092

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin-like ligase-substrate adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to lipopolysaccharide IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of SCF ubiquitin ligase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    F-box only protein 3
    Names
    F-box protein FBX3

    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_012175.4 → NP_036307.2  F-box only protein 3 isoform 1

      See identical proteins and their annotated locations for NP_036307.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1) which includes a highly acidic D/E-rich domain and two poly-R pieces at the C-terminus.
      Source sequence(s)
      BC039291, BC046110
      Consensus CDS
      CCDS7887.1
      UniProtKB/Swiss-Prot
      B3KY16, D3DR05, Q86X90, Q9H0V2, Q9NUX2, Q9UK99
      UniProtKB/TrEMBL
      Q59GS0
      Related
      ENSP00000265651.3, ENST00000265651.8
      Conserved Domains (3) summary
      pfam04379
      Location:294 → 383
      DUF525; ApaG domain
      pfam09346
      Location:121 → 249
      SMI1_KNR4; SMI1 / KNR4 family (SUKH-1)
      pfam12937
      Location:13 → 57
      F-box-like

    2. NM_033406.4 → NP_208385.1  F-box only protein 3 isoform 2

      See identical proteins and their annotated locations for NP_208385.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is divergent from variant 1 at the 3' terminus. It encodes a C-terminal truncated isoform, which lacks the D/E-rich domain and poly-Rs, as compared to isoform 1.
      Source sequence(s)
      AC113192, AF176702, AL049629, BC017107, BC039291
      Consensus CDS
      CCDS44566.1
      UniProtKB/TrEMBL
      Q59GS0
      Related
      ENSP00000408836.2, ENST00000448981.6
      Conserved Domains (3) summary
      smart00860
      Location:121 → 249
      SMI1_KNR4; SMI1 / KNR4 family
      pfam12937
      Location:13 → 57
      F-box-like; F-box-like
      cl01119
      Location:279 → 404
      DUF525; ApaG domain

    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

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      33740944..33774520 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011519980.2 → XP_011518282.1  F-box only protein 3 isoform X1

      Conserved Domains (3) summary
      pfam04379
      Location:294 → 383
      DUF525; Protein of unknown function (DUF525)
      pfam09346
      Location:121 → 249
      SMI1_KNR4; SMI1 / KNR4 family (SUKH-1)
      pfam12937
      Location:13 → 57
      F-box-like; F-box-like

    2. XM_047426752.1 → XP_047282708.1  F-box only protein 3 isoform X3

    3. XM_011519981.3 → XP_011518283.1  F-box only protein 3 isoform X2

      See identical proteins and their annotated locations for XP_011518283.1

      UniProtKB/TrEMBL
      Q59GS0
      Related
      ENSP00000431745.1, ENST00000534136.5
      Conserved Domains (3) summary
      pfam04379
      Location:294 → 383
      DUF525; ApaG domain
      pfam09346
      Location:121 → 249
      SMI1_KNR4; SMI1 / KNR4 family (SUKH-1)
      pfam12937
      Location:13 → 57
      F-box-like

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      33877954..33911529 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054368394.1 → XP_054224369.1  F-box only protein 3 isoform X1

    2. XM_054368396.1 → XP_054224371.1  F-box only protein 3 isoform X3

    3. XM_054368395.1 → XP_054224370.1  F-box only protein 3 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UK99.3 GenPept UniProtKB/Swiss-Prot:Q9UK99

    Gene LinkOut

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

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