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    FBXL3 F-box and leucine rich repeat protein 3 [ Homo sapiens (human) ]

    Gene ID: 26224, updated on 3-Nov-2024

    Summary

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    Official Symbol
    FBXL3provided by HGNC
    Official Full Name
    F-box and leucine rich repeat protein 3provided by HGNC
    Primary source
    HGNC:HGNC:13599
    See related
    Ensembl:ENSG00000005812 MIM:605653; AllianceGenome:HGNC:13599
    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
    FBL3; FBL3A; FBXL3A; IDDSFAS
    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 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 Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats and is localized in the nucleus. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 28.0), fat (RPKM 26.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FBXL3 in Genome Data Viewer
    Location:
    13q22.3
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (77005260..77027159, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (76222648..76250801, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (77579395..77601294, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5412 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5413 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5414 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:77566521-77567720 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7838 Neighboring gene DEAH-box helicase 9 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5415 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5417 Neighboring gene CLN5 intracellular trafficking protein Neighboring gene MYC binding protein 2 Neighboring gene MYCBP2 antisense RNA 1 Neighboring gene MYCBP2 antisense RNA 2 Neighboring gene NANOG hESC enhancer GRCh37_chr13:77692083-77692584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7839 Neighboring gene uncharacterized LOC124903184 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:77865534-77865737

    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. Biallelic variants in FBXL3 cause intellectual disability, delayed motor development and short stature. Ansar M, et al. Hum Mol Genet, 2019 Mar 15. PMID 30481285, Free PMC Article
    2. Highly Efficient Genome Editing via CRISPR/Cas9 to Create Clock Gene Knockout Cells. Korge S, et al. J Biol Rhythms, 2015 Oct. PMID 26243628
    3. [Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 via upregulating hsa-miR-18b-5p]. Luo J, et al. Nan Fang Yi Ke Da Xue Xue Bao, 2024 Jul 20. PMID 39051074, Free PMC Article
    4. FBXL3 is regulated by miRNA-4735-3p and suppresses cell proliferation and migration in non-small cell lung cancer. Wang D, et al. Pathol Res Pract, 2019 Feb. PMID 30594330
    5. miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer. Guo X, et al. Cell Death Dis, 2017 Jul 27. PMID 28749470, Free PMC Article

    See all (44) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. [Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 via upregulating hsa-miR-18b-5p].
      Title: [Tumor-associated fibroblasts promotes proliferation and migration of prostate cancer cells by suppressing FBXL3 via upregulating hsa-miR-18b-5p].
    2. we conclude that homozygous FBXL3 LoF variants likely cause autosomal recessive ID, short stature, developmental delay and facial dysmorphism in humans, and that the Cys358Arg FBXL3 variant likely adds the circadian phenotype because of abnormal interaction with CRY1 and CRY2
      Title: Biallelic variants in FBXL3 cause intellectual disability, delayed motor development and short stature.
    3. FBXL3 was regulated by miR-4735-3p and suppressed cell proliferation and invasion in non-small cell lung cancer.
      Title: FBXL3 is regulated by miRNA-4735-3p and suppresses cell proliferation and migration in non-small cell lung cancer.
    4. data indicate an oncogenic role of miR-181d in CRC by promoting glycolysis, and miR-181d/CRY2/FBXL3/c-myc feedback loop might be a therapeutic target for patients with CRC.
      Title: miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer.
    5. These results demonstrate that CRY2 stability controlled by FBXL3 plays a key role in the regulation of human sleep wake behavior.
      Title: A Cryptochrome 2 mutation yields advanced sleep phase in humans.
    6. CRY2 and FBXL3 cooperatively degrade c-MYC preventing the development of cancer.
      Title: CRY2 and FBXL3 Cooperatively Degrade c-MYC.
    7. Data show that CRISPR/Cas9 genome editing generated F-box and leucine-rich repeat protein 3 (Fbxl3) knockout in circadian clock model U2OS cells.
      Title: Highly Efficient Genome Editing via CRISPR/Cas9 to Create Clock Gene Knockout Cells.
    8. Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex.
      Title: Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein complex.
    9. Mutation in the Fbxl3 protein reveals distinct roles for CRY1 and CRY2 in the circadian molecular clockwork.
      Title: Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation.
    10. crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms
      Title: SCF(FBXL3) ubiquitin ligase targets cryptochromes at their cofactor pocket.
    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

    Associated conditions

    Description Tests
    Intellectual disability, short stature, facial anomalies, and joint dislocations
    MedGen: C1853507 OMIM: 606220 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD.
    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)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    contributes_to ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity NAS
    Non-traceable Author Statement
    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 entrainment of circadian clock by photoperiod IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in entrainment of circadian clock by photoperiod ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein destabilization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein ubiquitination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein ubiquitination NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of circadian rhythm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in rhythmic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nuclear body IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    part_of ubiquitin ligase complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    F-box/LRR-repeat protein 3
    Names
    F-box and leucine-rich repeat protein 3A
    F-box protein Fbl3a
    F-box/LRR-repeat protein 3A

    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_012158.4 → NP_036290.1  F-box/LRR-repeat protein 3

      See identical proteins and their annotated locations for NP_036290.1

      Status: REVIEWED

      Source sequence(s)
      AC001226
      Consensus CDS
      CCDS9457.1
      UniProtKB/Swiss-Prot
      B2RB04, Q9P122, Q9UKT7
      Related
      ENSP00000347834.5, ENST00000355619.10
      Conserved Domains (2) summary
      sd00034
      Location:174 → 199
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 77
      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

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      77005260..77027159 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005266336.2 → XP_005266393.1  F-box/LRR-repeat protein 3 isoform X1

      See identical proteins and their annotated locations for XP_005266393.1

      UniProtKB/Swiss-Prot
      B2RB04, Q9P122, Q9UKT7
      Conserved Domains (2) summary
      sd00034
      Location:174 → 199
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 77
      F-box-like

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      76222648..76250801 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054374424.1 → XP_054230399.1  F-box/LRR-repeat protein 3 isoform X2

    2. XM_054374423.1 → XP_054230398.1  F-box/LRR-repeat protein 3 isoform X1

      UniProtKB/Swiss-Prot
      B2RB04, Q9P122, Q9UKT7
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UKT7.1 GenPept UniProtKB/Swiss-Prot:Q9UKT7

    Gene LinkOut

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

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