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

Summary

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 several processes, including SCF-dependent proteasomal ubiquitin-dependent protein catabolic 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, Oct 2024]
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

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_000080.7 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: Mouse ENCODE transcriptome data 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CRY2 and FBXL3 cooperatively degrade c-MYC preventing the development of cancer.
Title: CRY2 and FBXL3 Cooperatively Degrade c-MYC.
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.
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.
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.
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.
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.
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.
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.
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)

Chemically induced (ENU) (5) 1 citation
Endonuclease-mediated (2)
Gene trapped (4) 1 citation
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH131875 (e-PCR)
- UniSTS:215158

AU041772 (e-PCR)
- UniSTS:160420

AW212966 (e-PCR)
- UniSTS:180713

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 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
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
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	ISO Inferred from Sequence Orthology more info
part_of SCF ubiquitin ligase complex	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
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)

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

Status: VALIDATED

Source sequence(s)

AC102815
NM_001424674.1 → NP_001411603.1 F-box/LRR-repeat protein 3 isoform 3

Status: VALIDATED

Source sequence(s)

AC102815

UniProtKB/TrEMBL

Q8BNS3
NM_001424675.1 → NP_001411604.1 F-box/LRR-repeat protein 3 isoform 3

Status: VALIDATED

Source sequence(s)

AC102815

UniProtKB/TrEMBL

Q8BNS3
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