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FBXL18 F-box and leucine rich repeat protein 18 [ Homo sapiens (human) ]

Gene ID: 80028, updated on 5-Mar-2024

Summary

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Official Symbol
FBXL18provided by HGNC
Official Full Name
F-box and leucine rich repeat protein 18provided by HGNC
Primary source
HGNC:HGNC:21874
See related
Ensembl:ENSG00000155034 MIM:609084; AllianceGenome:HGNC:21874
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
Fbl18
Summary
The protein encoded by this gene is a member of a family of proteins that contain an approximately 40-amino acid F-box motif. This motif is important for interaction with SKP1 and for targeting some proteins for degradation. The encoded protein has been shown to control the cellular level of FBXL7, a protein that induces mitotic arrest, by targeting it for polyubiquitylation and proteasomal degradation. Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains. [provided by RefSeq, Mar 2016]
Expression
Ubiquitous expression in brain (RPKM 2.3), fat (RPKM 1.2) and 24 other tissues See more
Orthologs
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Genomic context

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See FBXL18 in Genome Data Viewer
Location:
7p22.1
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (5454425..5513809, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (5571979..5631328, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (5494056..5553440, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene solute carrier family 29 member 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5350589-5351090 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5351091-5351590 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5362189-5362722 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5362723-5363256 Neighboring gene trinucleotide repeat containing 18 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5387551-5388392 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5390077-5390917 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5395754-5396256 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5421456-5422020 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5422021-5422584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25576 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5441055-5441556 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5443987-5444488 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5447331-5447920 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5447921-5448510 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5458249-5458998 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17914 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5467243-5467992 Neighboring gene long intergenic non-protein coding RNA 2983 Neighboring gene long intergenic non-protein coding RNA 3073 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5485342-5486174 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5491262-5491967 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5495336-5495836 Neighboring gene small nucleolar RNA U13 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5526631-5527352 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5528075-5528796 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25580 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25581 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5549867-5550805 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17916 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:5552897-5553483 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5553484-5554070 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5554071-5554656 Neighboring gene microRNA 589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25585 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25586 Neighboring gene uncharacterized LOC221946 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25587 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25588 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25590 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5567118-5567988 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5567989-5568858 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5568859-5569728 Neighboring gene actin beta

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. The F-box protein FBXL18 promotes glioma progression by promoting K63-linked ubiquitination of Akt. Zhang J, et al. FEBS Lett, 2017 Jan. PMID 27926990
  2. Fbxl18 targets LRRK2 for proteasomal degradation and attenuates cell toxicity. Ding X, et al. Neurobiol Dis, 2017 Feb. PMID 27890708, Free PMC Article
  3. F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7. Liu Y, et al. Cell Death Dis, 2015 Feb 5. PMID 25654763, Free PMC Article
  4. SCF(β-TRCP)-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway. Liu J, et al. Oncotarget, 2014 Feb 28. PMID 24657926, Free PMC Article
  5. Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. Brandler WM, et al. PLoS Genet, 2013. PMID 24068947, Free PMC Article

See all (41) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Study showed that LRRK2 phosphorylation is required for LRRK2 to bind to Fbxl18, and that this interaction is important for regulating the amount of LRRK2 via ubiquitination of LRRK2 by the SCFFbxl18 ubiquitin ligase and subsequent proteasomal degradation of LRRK2. We also show that LRRK2 can induce caspase 8 mediated cell death and that the degradation of LRRK2 mediated by Fbxl18 can prevent LRRK2-mediated toxicity.
    Title: Fbxl18 targets LRRK2 for proteasomal degradation and attenuates cell toxicity.
  2. FBXL18 plays an oncogenic role through promoting lysine 63-linked ubiquitination of Akt in glioma.
    Title: The F-box protein FBXL18 promotes glioma progression by promoting K63-linked ubiquitination of Akt.
  3. Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7 that may impact cellular processes involved in cell cycle progression.
    Title: F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
Submit: New GeneRIF Correction

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

EBI GWAS Catalog

Description
Common variants in left/right asymmetry genes and pathways are associated with relative hand skill.
EBI GWAS Catalog

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

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ10776, FLJ11467, FLJ26934, FLJ38075, FLJ41541

Gene Ontology Provided by GOA

Process Evidence Code Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
part_of SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
F-box/LRR-repeat protein 18

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_001321213.2 → NP_001308142.1  F-box/LRR-repeat protein 18 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC006483, AC092171
    UniProtKB/TrEMBL
    A0A994ENR3
    Conserved Domains (3) summary
    sd00034
    Location:345 → 384
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:33 → 75
    F-box-like; F-box-like
    pfam13900
    Location:763 → 779
    GVQW; Putative domain of unknown function

  2. NM_001363441.2 → NP_001350370.1  F-box/LRR-repeat protein 18 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC006483, AC092171
    Related
    ENSP00000415064.1, ENST00000415009.5
    Conserved Domains (2) summary
    sd00034
    Location:345 → 384
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:33 → 68
    F-box-like; F-box-like

  3. NM_001363442.2 → NP_001350371.1  F-box/LRR-repeat protein 18 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC006483, AC092171
    UniProtKB/TrEMBL
    A0A994ENR3
    Conserved Domains (2) summary
    sd00034
    Location:345 → 384
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:33 → 68
    F-box-like; F-box-like

  4. NM_001367780.1 → NP_001354709.1  F-box/LRR-repeat protein 18 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variant 6, encodes isoform 5.
    Source sequence(s)
    AC006483, AC092171
    UniProtKB/TrEMBL
    A0A994ENR3

  5. NM_001367781.1 → NP_001354710.1  F-box/LRR-repeat protein 18 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variant 5, encodes isoform 5.
    Source sequence(s)
    AC006483, AC092171
    UniProtKB/TrEMBL
    A0A994ENR3

  6. NM_024963.6 → NP_079239.3  F-box/LRR-repeat protein 18 isoform 2

    See identical proteins and their annotated locations for NP_079239.3

    Status: REVIEWED

    Source sequence(s)
    AA878073, AC006483, AC092171, AK294949, BC013435, DC307306
    Consensus CDS
    CCDS43546.1
    UniProtKB/Swiss-Prot
    A0A024R857, B3KTC9, B4DH63, H0Y6I6, Q96ME1, Q9BR90, Q9BTC7, Q9HAK7
    Related
    ENSP00000371805.3, ENST00000382368.8
    Conserved Domains (2) summary
    sd00034
    Location:345 → 384
    LRR_AMN1; leucine-rich repeat [structural motif]
    pfam12937
    Location:33 → 75
    F-box-like; 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

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    5454425..5513809 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    5571979..5631328 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96ME1.3 GenPept UniProtKB/Swiss-Prot:Q96ME1

Gene LinkOut

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