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    Fbxl3 F-box and leucine-rich repeat protein 3 [ Mus musculus (house mouse) ]

    Gene ID: 50789, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Fbxl3provided by MGI
    Official Full Name
    F-box and leucine-rich repeat protein 3provided by MGI
    Primary source
    MGI:MGI:1354702
    See related
    Ensembl:ENSMUSG00000022124 AllianceGenome:MGI:1354702
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    FBK; Ovtm; Fbl3a; Fbxl3a; Play68
    Summary
    Contributes to ubiquitin-protein transferase activity. Involved in cellular protein metabolic process; entrainment of circadian clock by photoperiod; and protein destabilization. Located in cytosol and nucleus. Is expressed in embryo; extraembryonic component; inner cell mass; and trophectoderm. Orthologous to human FBXL3 (F-box and leucine rich repeat protein 3). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in cerebellum adult (RPKM 14.1), bladder adult (RPKM 13.9) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    14 E2.3; 14 51.73 cM
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 14 NC_000080.7 (103318470..103337016, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 14 NC_000080.6 (103080239..103099566, complement)

    Chromosome 14 - NC_000080.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_37495 Neighboring gene STARR-positive B cell enhancer mm9_chr14:103464914-103465215 Neighboring gene STARR-positive B cell enhancer ABC_E7347 Neighboring gene predicted gene, 41236 Neighboring gene STARR-seq mESC enhancer starr_37499 Neighboring gene STARR-positive B cell enhancer ABC_E11579 Neighboring gene STARR-seq mESC enhancer starr_37500 Neighboring gene ceroid-lipofuscinosis, neuronal 5 Neighboring gene STARR-seq mESC enhancer starr_37501 Neighboring gene MYC binding protein 2, E3 ubiquitin protein ligase Neighboring gene RIKEN cDNA 1700087I21 gene Neighboring gene STARR-positive B cell enhancer mm9_chr14:103745967-103746268 Neighboring gene CapStarr-seq enhancer MGSCv37_chr14:103748726-103748913 Neighboring gene STARR-positive B cell enhancer ABC_E10839

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. The after-hours circadian mutant has reduced phenotypic plasticity in behaviors at multiple timescales and in sleep homeostasis. Maggi S, et al. Sci Rep, 2017 Dec 19. PMID 29259298, Free PMC Article
    2. Suppressed cellular oscillations in after-hours mutant mice are associated with enhanced circadian phase-resetting. Guilding C, et al. J Physiol, 2013 Feb 15. PMID 23207594, Free PMC Article
    3. Reduced anxiety and depression-like behaviours in the circadian period mutant mouse afterhours. Keers R, et al. PLoS One, 2012. PMID 22719873, Free PMC Article
    4. Delayed Cryptochrome Degradation Asymmetrically Alters the Daily Rhythm in Suprachiasmatic Clock Neuron Excitability. Wegner S, et al. J Neurosci, 2017 Aug 16. PMID 28698388, Free PMC Article
    5. Tuning the period of the mammalian circadian clock: additive and independent effects of CK1εTau and Fbxl3Afh mutations on mouse circadian behavior and molecular pacemaking. Maywood ES, et al. J Neurosci, 2011 Jan 26. PMID 21273438, Free PMC Article

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CRY2 and FBXL3 cooperatively degrade c-MYC preventing the development of cancer.
      Title: CRY2 and FBXL3 Cooperatively Degrade c-MYC.
    2. 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.
    3. By analyzing the Fbxl3 and Cryptochrome 1 double-mutant mice, we found that FBXL3 also regulates the amplitudes of E-box-driven gene expression.
      Title: Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock.
    4. 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.
    5. FBXL21 plays a dual role: protecting CRY 1/2 proteins (CRY) from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm.
      Title: Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.
    6. results are consistent with previous studies of mutants with extended circadian periods and suggest that disruption of FBXL3 is associated with mania-like behaviours in both mice and humans
      Title: Reduced anxiety and depression-like behaviours in the circadian period mutant mouse afterhours.
    7. In Ovtm mice, expression of the PERIOD proteins is reduced; however, the CRY proteins are unchanged; the loss of FBXL3 function leads to a stabilization of the CRY proteins, which leads to a global transcriptional repression of the Per and Cry genes.
      Title: Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression.
    8. studies reveal a central role for Fbxl3 in mammalian circadian timekeeping
      Title: The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period.
    9. study demonstrates that the SCF(Fbxl3)ubiquitin ligase controls the oscillations of the circadian clock by mediating the degradation of Cry1 and Cry2 proteins
      Title: SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    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 MGI

    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 
    contributes_to ubiquitin-protein transferase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    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 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    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 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein destabilization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of circadian rhythm IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of circadian rhythm ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within 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 ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear body ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    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/LRR-repeat protein 3A
    protein after-hours
    protein overtime

    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_001347600.2 → NP_001334529.1  F-box/LRR-repeat protein 3 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The encoded isoform (2) has the same N- and C-termini, but is shorter than isoform 1.
      Source sequence(s)
      AC102815
      Consensus CDS
      CCDS84159.1
      UniProtKB/TrEMBL
      Q3TJJ7
      Conserved Domains (2) summary
      sd00034
      Location:126 → 151
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 69
      F-box-like

    2. NM_001347601.2 → NP_001334530.1  F-box/LRR-repeat protein 3 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The encoded isoform (2) has the same N- and C-termini, but is shorter than isoform 1.
      Source sequence(s)
      AC102815
      Consensus CDS
      CCDS84159.1
      UniProtKB/TrEMBL
      Q3TJJ7
      Related
      ENSMUSP00000115843.2, ENSMUST00000132004.8
      Conserved Domains (2) summary
      sd00034
      Location:126 → 151
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 69
      F-box-like

    3. NM_001360341.2 → NP_001347270.1  F-box/LRR-repeat protein 3 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC102815
      Consensus CDS
      CCDS27315.1
      UniProtKB/Swiss-Prot
      Q80V32, Q8C4V4, Q8K1W0, Q9QXW1
      UniProtKB/TrEMBL
      Q3TJJ7, Q5PRF6
      Related
      ENSMUSP00000116044.2, ENSMUST00000145693.8
      Conserved Domains (2) summary
      sd00034
      Location:174 → 199
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 77
      F-box-like; F-box-like

    4. NM_001360342.2 → NP_001347271.1  F-box/LRR-repeat protein 3 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC102815
      Consensus CDS
      CCDS27315.1
      UniProtKB/Swiss-Prot
      Q80V32, Q8C4V4, Q8K1W0, Q9QXW1
      UniProtKB/TrEMBL
      Q3TJJ7, Q5PRF6
      Conserved Domains (2) summary
      sd00034
      Location:174 → 199
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 77
      F-box-like; F-box-like

    5. NM_001424673.1 → NP_001411602.1  F-box/LRR-repeat protein 3 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC102815

    6. NM_001424674.1 → NP_001411603.1  F-box/LRR-repeat protein 3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC102815
      UniProtKB/TrEMBL
      Q8BNS3

    7. NM_001424675.1 → NP_001411604.1  F-box/LRR-repeat protein 3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC102815
      UniProtKB/TrEMBL
      Q8BNS3

    8. NM_015822.4 → NP_056637.1  F-box/LRR-repeat protein 3 isoform 1

      See identical proteins and their annotated locations for NP_056637.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC102815
      Consensus CDS
      CCDS27315.1
      UniProtKB/Swiss-Prot
      Q80V32, Q8C4V4, Q8K1W0, Q9QXW1
      UniProtKB/TrEMBL
      Q3TJJ7, Q5PRF6
      Related
      ENSMUSP00000022720.9, ENSMUST00000022720.15
      Conserved Domains (2) summary
      sd00034
      Location:174 → 199
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:36 → 77
      F-box-like; F-box-like

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000080.7 Reference GRCm39 C57BL/6J

      Range
      103318470..103337016 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8C4V4.1 GenPept UniProtKB/Swiss-Prot:Q8C4V4

    Gene LinkOut

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

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