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

Gene ID: 26224, updated on 5-Mar-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
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Genomic context

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Location:
13q22.3
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (77005260..77027159, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (76222648..76250801, complement)
105.20220307 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
  • 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. 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
  4. 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
  5. A Cryptochrome 2 mutation yields advanced sleep phase in humans. Hirano A, et al. Elife, 2016 Aug 16. PMID 27529127, Free PMC Article

See all (39) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. CRY2 and FBXL3 cooperatively degrade c-MYC preventing the development of cancer.
    Title: CRY2 and FBXL3 Cooperatively Degrade c-MYC.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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

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_2023_10

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

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