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

    Gene ID: 25827, updated on 27-Nov-2024

    Summary

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    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
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    Genomic context

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    See FBXL2 in Genome Data Viewer
    Location:
    3p22.3
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (33277025..33422698)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (33278817..33424454)
    RS_2024_09 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

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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. 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. Crystal structure and interaction studies of the human FBxo3 ApaG domain. Krzysiak TC, et al. FEBS J, 2016 Jun. PMID 27010866, Free PMC Article
    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. FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance. Li F, et al. Oncogene, 2023 Jan. PMID 36460773
    5. Identification of a novel Skp2-like mammalian protein containing F-box and leucine-rich repeats. Ilyin GP, et al. FEBS Lett, 1999 Oct 1. PMID 10508920

    See all (48) 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

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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

    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

    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

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    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)

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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_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_2024_08

    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.

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