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

Gene ID: 50789, updated on 8-Dec-2022

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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See Fbxl3 in Genome Data Viewer
Location:
14; 14 E2.3
Exon count:
6
Annotation release Status Assembly Chr Location
109 current GRCm39 (GCF_000001635.27) 14 NC_000080.7 (103317675..103337036, 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 predicted gene, 41236 Neighboring gene ceroid-lipofuscinosis, neuronal 5 Neighboring gene MYC binding protein 2, E3 ubiquitin protein ligase Neighboring gene predicted gene, 34758

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

See citations in PubMed for homologs of this gene provided by HomoloGene

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.
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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
 PubMed 
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
 PubMed 
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
 PubMed 
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
 PubMed 
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
 PubMed 
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_001347600.1 → 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.Variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AC102815, AK142007, BY146960, BY276318
    Consensus CDS
    CCDS84159.1
    UniProtKB/TrEMBL
    Q5PRF6
    Conserved Domains (2) summary
    sd00034
    Location:126 → 151
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:36 → 69
    F-box-like

  2. NM_001347601.1 → 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. Variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AC102815, AK142007, BY276318
    Consensus CDS
    CCDS84159.1
    UniProtKB/TrEMBL
    Q5PRF6
    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_001360341.1 → NP_001347270.1  F-box/LRR-repeat protein 3 isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC102815, AK142007, BC067203
    Consensus CDS
    CCDS27315.1
    UniProtKB/Swiss-Prot
    Q9QXW1
    UniProtKB/TrEMBL
    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_001360342.1 → NP_001347271.1  F-box/LRR-repeat protein 3 isoform 1

    Status: VALIDATED

    Source sequence(s)
    AC102815, AK142007, BC067203, BY146960
    Consensus CDS
    CCDS27315.1
    UniProtKB/Swiss-Prot
    Q9QXW1
    UniProtKB/TrEMBL
    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_015822.3 → 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)
    AK142007, BY787665
    Consensus CDS
    CCDS27315.1
    UniProtKB/Swiss-Prot
    Q8C4V4, Q9QXW1
    UniProtKB/TrEMBL
    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: Mus musculus Annotation Release 109 details...Open this link in a new tab

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
    103317675..103337036 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006519240.5 → XP_006519303.1  F-box/LRR-repeat protein 3 isoform X1

    See identical proteins and their annotated locations for XP_006519303.1

    UniProtKB/Swiss-Prot
    Q8C4V4
    Conserved Domains (2) summary
    sd00034
    Location:126 → 151
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:36 → 69
    F-box-like

  2. XM_006519243.4 → XP_006519306.1  F-box/LRR-repeat protein 3 isoform X2

    See identical proteins and their annotated locations for XP_006519306.1

    UniProtKB/TrEMBL
    Q8BNS3
    Conserved Domains (1) summary
    sd00034
    Location:22 → 47
    LRR_AMN1; leucine-rich repeat [structural motif]
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8C4V4.1 GenPept UniProtKB/Swiss-Prot:Q8C4V4

Gene LinkOut

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