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

Summary

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

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_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH119624 (e-PCR)
- UniSTS:133942

RH131875 (e-PCR)
- UniSTS:215158

WI-19996 (e-PCR)
- UniSTS:2298

A006Y41 (e-PCR)
- UniSTS:12031

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)

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

NC_000013.11 Reference GRCh38.p14 Primary Assembly

Range

77005260..77027159 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_060937.1 Alternate T2T-CHM13v2.0

Range

76222648..76250801 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054374424.1 → XP_054230399.1 F-box/LRR-repeat protein 3 isoform X2
XM_054374423.1 → XP_054230398.1 F-box/LRR-repeat protein 3 isoform X1

UniProtKB/Swiss-Prot

B2RB04, Q9P122, Q9UKT7