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

Gene ID: 26234, updated on 3-Apr-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
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Genomic context

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Location:
4p15.32
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (15604381..15681569, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (15586272..15663882, complement)
105.20220307 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
  • 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. 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. Cho YA, et al. Cancer Genomics Proteomics, 2023 May-Jun. PMID 37093682, Free PMC Article
  2. Redox sensing molecular mechanism of an iron metabolism regulatory protein FBXL5. Wei Y, et al. Arch Biochem Biophys, 2017 Feb 15. PMID 28131773
  3. Hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5) communicates cellular iron and oxygen availability by distinct mechanisms. Chollangi S, et al. J Biol Chem, 2012 Jul 6. PMID 22648410, Free PMC Article
  4. Structural and molecular characterization of iron-sensing hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5). Thompson JW, et al. J Biol Chem, 2012 Mar 2. PMID 22253436, Free PMC Article
  5. Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma. Park CK, et al. Cancer Res Treat, 2021 Oct. PMID 33735560, Free PMC Article

See all (55) citations in PubMed

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 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 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_2023_10

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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