U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

FBXL2 F-box and leucine rich repeat protein 2 [ Homo sapiens (human) ]

Gene ID: 25827, updated on 11-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
FBXL2provided by HGNC
Official Full Name
F-box and leucine rich repeat protein 2provided by HGNC
Primary source
HGNC:HGNC:13598
See related
Ensembl:ENSG00000153558 MIM:605652; AllianceGenome:HGNC:13598
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
FBL2; FBL3
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 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
Expression
Broad expression in brain (RPKM 5.0), testis (RPKM 4.2) and 22 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See FBXL2 in Genome Data Viewer
Location:
3p22.3
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (33277025..33422698)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (33278817..33424454)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (33318517..33464190)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14183 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14184 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:33156217-33157208 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:33157792-33157940 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19646 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19647 Neighboring gene cartilage associated protein Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:33194307-33195506 Neighboring gene sushi domain containing 5 Neighboring gene Sharpr-MPRA regulatory region 10469 Neighboring gene uncharacterized LOC124909362 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14185 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:33318889-33319056 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14186 Neighboring gene MPRA-validated peak4597 silencer Neighboring gene MPRA-validated peak4598 silencer Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:33467587-33468144 Neighboring gene RNA, U7 small nuclear 110 pseudogene Neighboring gene upstream binding protein 1 Neighboring gene Sharpr-MPRA regulatory region 11903 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:33480902-33481136 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:33481355-33481854 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14190 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19648 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19649 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:33487995-33488496 Neighboring gene uncharacterized LOC124909363 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:33489631-33490130 Neighboring gene NANOG hESC enhancer GRCh37_chr3:33504525-33505078 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:33508920-33510119 Neighboring gene RNA, 5S ribosomal pseudogene 128

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Neuronal expression of F-box and leucine-rich-repeat protein 2 decreases over Braak stages in the brains of Alzheimer's disease patients. Watanabe T, et al. Neurodegener Dis, 2013. PMID 22455980
  2. FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance. Li F, et al. Oncogene, 2023 Jan. PMID 36460773
  3. O-GlcNAcylation-mediated degradation of FBXL2 stabilizes FOXM1 to induce cancer progression. Ueda Y, et al. Biochem Biophys Res Commun, 2020 Jan 15. PMID 31679690
  4. Crystal structure and interaction studies of the human FBxo3 ApaG domain. Krzysiak TC, et al. FEBS J, 2016 Jun. PMID 27010866, Free PMC Article
  5. FOSL1 promotes tumorigenesis in colorectal carcinoma by mediating the FBXL2/Wnt/β-catenin axis via Smurf1. Liu Y, et al. Pharmacol Res, 2021 Mar. PMID 33450386

See all (44) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance.
    Title: FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance.
  2. FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
    Title: FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
  3. Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction with cis-Acting Regulatory Elements within the Fbxl2 Gene Promoter.
    Title: Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction with cis-Acting Regulatory Elements within the Fbxl2 Gene Promoter.
  4. The interaction with FBXL2 and ubiquitination of FOXM1 were reduced by elevated O-GlcNAcylation. Elevated O-GlcNAcylation contributes to cancer progression by suppressing FBXL2-mediated degradation of FOXM1.
    Title: O-GlcNAcylation-mediated degradation of FBXL2 stabilizes FOXM1 to induce cancer progression.
  5. miR-346-5p promoted colorectal cancer cell growth in vitro and in vivo by targeting FBXL2 and activating the beta-catenin signaling.
    Title: MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the β-catenin signaling pathway.
  6. PTEN counteracts FBXL2 to promote IP3R3- and Ca(2+)-mediated apoptosis limiting tumour growth
    Title: PTEN counteracts FBXL2 to promote IP3R3- and Ca(2+)-mediated apoptosis limiting tumour growth.
  7. these results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.
    Title: F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1.
  8. FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation.
    Title: Lipopolysaccharide Primes the NALP3 Inflammasome by Inhibiting Its Ubiquitination and Degradation Mediated by the SCFFBXL2 E3 Ligase.
  9. FBXL2 mediates the ubiquitylation and degradation of p85beta on cell membranes.
    Title: FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade.
  10. These results suggested that the involvement of the reduction of FBL2 level is related to AD progression.
    Title: Neuronal expression of F-box and leucine-rich-repeat protein 2 decreases over Braak stages in the brains of Alzheimer's disease patients.
Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • DKFZp564P0622

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calmodulin binding IEA
Inferred from Electronic Annotation
more info
  
enables phosphatidylinositol 3-kinase regulatory subunit binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein phosphatase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-like ligase-substrate adaptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in modulation by host of viral RNA genome replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of NLRP3 inflammasome complex assembly IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein modification process TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein monoubiquitination IEA
Inferred from Electronic Annotation
more info
  
involved_in protein ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of autophagy IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
part_of SCF ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

Go to the top of the page Help
Preferred Names
F-box/LRR-repeat protein 2
Names
F-box protein FBL2/FBL3
F-box protein containing leucine-rich repeats

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_001349316.2 → NP_001336245.1  F-box/LRR-repeat protein 2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) encodes the longest isoform (3).
    Source sequence(s)
    AC122176, AC123900
    UniProtKB/TrEMBL
    B3KM70
    Conserved Domains (3) summary
    sd00034
    Location:106 → 131
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:15 → 56
    F-box-like; F-box-like
    cl28166
    Location:168 → 398
    AMN1; Antagonist of mitotic exit network protein 1

  2. NM_001349319.2 → NP_001336248.1  F-box/LRR-repeat protein 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variants 5 and 6, encodes isoform 4.
    Source sequence(s)
    AC122176, AC123900
    Conserved Domains (2) summary
    cd09293
    Location:63 → 293
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  3. NM_001349320.2 → NP_001336249.1  F-box/LRR-repeat protein 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variants 4 and 6, encodes isoform 4.
    Source sequence(s)
    AC122176, AC123900
    Conserved Domains (2) summary
    cd09293
    Location:63 → 293
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  4. NM_001349321.2 → NP_001336250.1  F-box/LRR-repeat protein 2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variants 4 and 5, encodes isoform 4.
    Source sequence(s)
    AC122176, AC123900
    Conserved Domains (2) summary
    cd09293
    Location:63 → 293
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  5. NM_001349322.2 → NP_001336251.1  F-box/LRR-repeat protein 2 isoform 5 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) encodes isoform 5.
    Source sequence(s)
    AC122176, AC123900
    UniProtKB/TrEMBL
    B4E1B8
    Conserved Domains (2) summary
    cd09293
    Location:84 → 283
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:22 → 47
    LRR_AMN1; leucine-rich repeat [structural motif]

  6. NM_001349323.2 → NP_001336252.1  F-box/LRR-repeat protein 2 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variants 9, 10, and 11, encodes isoform 6.
    Source sequence(s)
    AC122176, AC123900
    UniProtKB/TrEMBL
    B4DMM3
    Conserved Domains (2) summary
    cd09293
    Location:63 → 262
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  7. NM_001349324.2 → NP_001336253.1  F-box/LRR-repeat protein 2 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 8, 10, and 11, encodes isoform 6.
    Source sequence(s)
    AC122176, AC123900
    UniProtKB/TrEMBL
    B4DMM3
    Conserved Domains (2) summary
    cd09293
    Location:63 → 262
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  8. NM_001349325.2 → NP_001336254.1  F-box/LRR-repeat protein 2 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 8, 9, and 11, encodes isoform 6.
    Source sequence(s)
    AC122176, AC123900
    UniProtKB/TrEMBL
    B4DMM3
    Conserved Domains (2) summary
    cd09293
    Location:63 → 262
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  9. NM_001349326.2 → NP_001336255.1  F-box/LRR-repeat protein 2 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (11), as well as variants 8, 9, and 10, encodes isoform 6.
    Source sequence(s)
    AC122176, AC123900
    UniProtKB/TrEMBL
    B4DMM3
    Conserved Domains (2) summary
    cd09293
    Location:63 → 262
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:27 → 52
    LRR_AMN1; leucine-rich repeat [structural motif]

  10. NM_012157.5 → NP_036289.3  F-box/LRR-repeat protein 2 isoform 1

    See identical proteins and their annotated locations for NP_036289.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1.
    Source sequence(s)
    AC122176, AK001271
    Consensus CDS
    CCDS2658.1
    UniProtKB/Swiss-Prot
    B4DQV0, E9PD06, Q6IAN3, Q9NVQ8, Q9UK27, Q9UKA5, Q9UKC9, Q9Y3Y9
    UniProtKB/TrEMBL
    B3KM70
    Related
    ENSP00000417601.1, ENST00000484457.6
    Conserved Domains (3) summary
    cd09293
    Location:168 → 367
    AMN1; Antagonist of mitotic exit network protein 1
    sd00034
    Location:106 → 131
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:15 → 56
    F-box-like

RNA

  1. NR_146121.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  2. NR_146122.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  3. NR_146123.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  4. NR_146124.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  5. NR_146125.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  6. NR_146126.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  7. NR_146127.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  8. NR_146128.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900
    Related
    ENST00000463736.5

  9. NR_146129.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  10. NR_146130.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  11. NR_146131.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  12. NR_146132.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  13. NR_146133.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  14. NR_146134.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

  15. NR_146135.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC122176, AC123900

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_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    33277025..33422698
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_007095659.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    33278817..33424454
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054346016.1 → XP_054201991.1  F-box/LRR-repeat protein 2 isoform X1

  2. XM_054346017.1 → XP_054201992.1  F-box/LRR-repeat protein 2 isoform X2

RNA

  1. XR_008486695.1 RNA Sequence

  2. XR_008486694.1 RNA Sequence

  3. XR_008486696.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001171713.2: Suppressed sequence

    Description
    NM_001171713.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9UKC9.3 GenPept UniProtKB/Swiss-Prot:Q9UKC9

Gene LinkOut

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

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous