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    FBXL5 F-box and leucine rich repeat protein 5 [ Homo sapiens (human) ]

    Gene ID: 26234, updated on 3-Nov-2024

    Summary

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    Official Symbol
    FBXL5provided by HGNC
    Official Full Name
    F-box and leucine rich repeat protein 5provided by HGNC
    Primary source
    HGNC:HGNC:13602
    See related
    Ensembl:ENSG00000118564 MIM:605655; AllianceGenome:HGNC:13602
    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
    FBL4; FBL5; FLR1
    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. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2010]
    Expression
    Ubiquitous expression in kidney (RPKM 49.5), fat (RPKM 39.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See FBXL5 in Genome Data Viewer
    Location:
    4p15.32
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (15604381..15681569, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (15586272..15663882, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (15606004..15656980, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene coiled-coil and C2 domain containing 2A Neighboring gene uncharacterized LOC124900672 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr4:15545311-15545892 Neighboring gene uncharacterized LOC124900671 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:15637196-15637392 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:15648787-15649012 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15296 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15298 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15297 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:15656873-15657050 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21340 Neighboring gene family with sequence similarity 200 member B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21341 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21342 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21343 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:15696758-15697354 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15300 Neighboring gene bone marrow stromal cell antigen 1 Neighboring gene ribosomal protein L10a pseudogene 7 Neighboring gene PFDN1 pseudogene 2

    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 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?
    1. FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB.
      Title: FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB.
    2. Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.
      Title: Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.
    3. Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma.
      Title: Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma.
    4. This study has identified an iron-sulfur cluster within FBXL5, which promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.
      Title: FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster.
    5. Dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human hepatocellular carcinoma, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.
      Title: Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.
    6. We demonstrate that the CIA-targeting complex promotes the ability of FBXL5 to degrade iron regulatory proteins. In addition, the FBXL5-CIA-targeting complex interaction is regulated by oxygen (O2) tension displaying a robust association in 21% O2 that is severely diminished in 1% O2 and contributes to O2-dependent regulation of IRP degradation
      Title: An Oxygen-Dependent Interaction between FBXL5 and the CIA-Targeting Complex Regulates Iron Homeostasis.
    7. MiR-1306-3p directly targets FBXL5 and modulates FBXL5-meadiated snail protein stability in hepatocellular carcinoma.
      Title: miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma through suppressing snail degradation.
    8. this study demonstrated that FBXL5 functioned as an oncogene in the progression of colon cancer through regulating PTEN/PI3K/AKT signaling
      Title: F-box and leucine-rich repeat protein 5 promotes colon cancer progression by modulating PTEN/PI3K/AKT signaling pathway.
    9. Transcriptomic analysis shows downregulation of FBXL5 expression in HSCs of patients with myelodysplastic syndrome.
      Title: Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells.
    10. regulatory circuit involving FBXL5 and CIA acts through both IRPs to control iron metabolism and promote optimal cell growth
      Title: A synergistic role of IRP1 and FBXL5 proteins in coordinating iron metabolism during cell proliferation.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    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 Variation Viewer (GRCh37.p13)

    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 2 iron, 2 sulfur cluster binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables iron ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    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 intracellular iron ion homeostasis IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in intracellular iron ion homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in multicellular organismal-level iron ion homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    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 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 5
    Names
    F-box protein FBL4/FBL5
    p45SKP2-like protein

    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.

    Genomic

    1. NG_047143.2 RefSeqGene

      Range
      31212..82188
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001193534.2 → NP_001180463.1  F-box/LRR-repeat protein 5 isoform 3

      See identical proteins and their annotated locations for NP_001180463.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
      Source sequence(s)
      AC116651, AF142481, AF199420, AI858616, BC030656, BF432189
      UniProtKB/TrEMBL
      H0Y9Y0
      Conserved Domains (4) summary
      cd09293
      Location:353 → 407
      AMN1; Antagonist of mitotic exit network protein 1
      cd12109
      Location:7 → 160
      Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins
      sd00034
      Location:331 → 356
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:204 → 248
      F-box-like; F-box-like

    2. NM_001193535.2 → NP_001180464.1  F-box/LRR-repeat protein 5 isoform 4

      See identical proteins and their annotated locations for NP_001180464.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.
      Source sequence(s)
      AC116651, AI858616, BF432189, BX537957
      Consensus CDS
      CCDS54745.1
      UniProtKB/TrEMBL
      H0Y9Y0
      Related
      ENSP00000408679.2, ENST00000412094.6
      Conserved Domains (4) summary
      cd09293
      Location:337 → 391
      AMN1; Antagonist of mitotic exit network protein 1
      cd12109
      Location:7 → 143
      Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins
      sd00034
      Location:315 → 340
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:188 → 232
      F-box-like; F-box-like

    3. NM_012161.4 → NP_036293.1  F-box/LRR-repeat protein 5 isoform 1

      See identical proteins and their annotated locations for NP_036293.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC116651, AF142481, AI858616, BC030656, BF432189
      Consensus CDS
      CCDS3415.1
      UniProtKB/Swiss-Prot
      A8MSK4, B4DIB5, Q4W5A8, Q8NHP3, Q9NXN2, Q9P0I0, Q9P0X5, Q9UJT7, Q9UKA1, Q9UKC8
      UniProtKB/TrEMBL
      H0Y9Y0
      Related
      ENSP00000344866.3, ENST00000341285.8
      Conserved Domains (4) summary
      cd09293
      Location:354 → 408
      AMN1; Antagonist of mitotic exit network protein 1
      cd12109
      Location:7 → 160
      Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins
      sd00034
      Location:332 → 357
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:205 → 249
      F-box-like; F-box-like

    RNA

    1. NR_036464.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC116651, AI858616, BC012320, BC030656, BF432189
      Related
      ENST00000511441.5

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      15604381..15681569 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047450056.1 → XP_047306012.1  F-box/LRR-repeat protein 5 isoform X1

    2. XM_047450055.1 → XP_047306011.1  F-box/LRR-repeat protein 5 isoform X1

    3. XM_047450059.1 → XP_047306015.1  F-box/LRR-repeat protein 5 isoform X2

    4. XM_047450050.1 → XP_047306006.1  F-box/LRR-repeat protein 5 isoform X1

    5. XM_011513831.3 → XP_011512133.1  F-box/LRR-repeat protein 5 isoform X2

      UniProtKB/TrEMBL
      H0Y9Y0
      Conserved Domains (4) summary
      cd09293
      Location:318 → 372
      AMN1; Antagonist of mitotic exit network protein 1
      cd12109
      Location:9 → 124
      Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins
      sd00034
      Location:296 → 321
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:169 → 213
      F-box-like; F-box-like

    6. XM_047450054.1 → XP_047306010.1  F-box/LRR-repeat protein 5 isoform X1

    7. XM_047450053.1 → XP_047306009.1  F-box/LRR-repeat protein 5 isoform X1

    8. XM_047450058.1 → XP_047306014.1  F-box/LRR-repeat protein 5 isoform X2

    9. XM_047450049.1 → XP_047306005.1  F-box/LRR-repeat protein 5 isoform X1

    10. XM_047450057.1 → XP_047306013.1  F-box/LRR-repeat protein 5 isoform X2

    11. XM_006713959.4 → XP_006714022.1  F-box/LRR-repeat protein 5 isoform X1

      UniProtKB/TrEMBL
      H0Y9Y0
      Conserved Domains (4) summary
      cd09293
      Location:335 → 389
      AMN1; Antagonist of mitotic exit network protein 1
      cd12109
      Location:10 → 141
      Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins
      sd00034
      Location:313 → 338
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:186 → 230
      F-box-like; F-box-like

    12. XM_047450060.1 → XP_047306016.1  F-box/LRR-repeat protein 5 isoform X2

    13. XM_017008019.3 → XP_016863508.1  F-box/LRR-repeat protein 5 isoform X3

      UniProtKB/TrEMBL
      H0Y9Y0
      Conserved Domains (4) summary
      cd09293
      Location:299 → 353
      AMN1; Antagonist of mitotic exit network protein 1
      cd12109
      Location:1 → 105
      Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins
      sd00034
      Location:277 → 302
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:150 → 194
      F-box-like; F-box-like

    14. XM_047450061.1 → XP_047306017.1  F-box/LRR-repeat protein 5 isoform X3

    15. XM_047450051.1 → XP_047306007.1  F-box/LRR-repeat protein 5 isoform X1

    16. XM_047450052.1 → XP_047306008.1  F-box/LRR-repeat protein 5 isoform X1

    17. XM_011513833.3 → XP_011512135.1  F-box/LRR-repeat protein 5 isoform X4

      UniProtKB/TrEMBL
      H0Y9Y0
      Conserved Domains (4) summary
      cd09293
      Location:282 → 336
      AMN1; Antagonist of mitotic exit network protein 1
      sd00034
      Location:260 → 285
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam12937
      Location:133 → 177
      F-box-like; F-box-like
      cl15774
      Location:20 → 88
      Hemerythrin-like; Hemerythrin family

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      15586272..15663882 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054349670.1 → XP_054205645.1  F-box/LRR-repeat protein 5 isoform X2

    2. XM_054349654.1 → XP_054205629.1  F-box/LRR-repeat protein 5 isoform X1

    3. XM_054349655.1 → XP_054205630.1  F-box/LRR-repeat protein 5 isoform X1

    4. XM_054349668.1 → XP_054205643.1  F-box/LRR-repeat protein 5 isoform X2

    5. XM_054349652.1 → XP_054205627.1  F-box/LRR-repeat protein 5 isoform X1

    6. XM_054349666.1 → XP_054205641.1  F-box/LRR-repeat protein 5 isoform X2

    7. XM_054349656.1 → XP_054205631.1  F-box/LRR-repeat protein 5 isoform X1

    8. XM_054349660.1 → XP_054205635.1  F-box/LRR-repeat protein 5 isoform X1

    9. XM_054349659.1 → XP_054205634.1  F-box/LRR-repeat protein 5 isoform X1

    10. XM_054349669.1 → XP_054205644.1  F-box/LRR-repeat protein 5 isoform X2

    11. XM_054349653.1 → XP_054205628.1  F-box/LRR-repeat protein 5 isoform X1

    12. XM_054349665.1 → XP_054205640.1  F-box/LRR-repeat protein 5 isoform X2

    13. XM_054349658.1 → XP_054205633.1  F-box/LRR-repeat protein 5 isoform X1

    14. XM_054349657.1 → XP_054205632.1  F-box/LRR-repeat protein 5 isoform X1

    15. XM_054349664.1 → XP_054205639.1  F-box/LRR-repeat protein 5 isoform X1

    16. XM_054349667.1 → XP_054205642.1  F-box/LRR-repeat protein 5 isoform X2

    17. XM_054349661.1 → XP_054205636.1  F-box/LRR-repeat protein 5 isoform X1

    18. XM_054349663.1 → XP_054205638.1  F-box/LRR-repeat protein 5 isoform X1

    19. XM_054349671.1 → XP_054205646.1  F-box/LRR-repeat protein 5 isoform X3

    20. XM_054349662.1 → XP_054205637.1  F-box/LRR-repeat protein 5 isoform X1

    21. XM_054349672.1 → XP_054205647.1  F-box/LRR-repeat protein 5 isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UKA1.2 GenPept UniProtKB/Swiss-Prot:Q9UKA1

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