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Aliases for FBXL2 Gene

Aliases for FBXL2 Gene

  • F-Box And Leucine Rich Repeat Protein 2 2 3 5
  • F-Box Protein FBL2/FBL3 3 4
  • FBL2 3 4
  • FBL3 3 4
  • F-Box Protein Containing Leucine-Rich Repeats 3
  • F-Box And Leucine-Rich Repeat Protein 2 4
  • F-Box/LRR-Repeat Protein 2 3

External Ids for FBXL2 Gene

Previous GeneCards Identifiers for FBXL2 Gene

  • GC03P032625
  • GC03P033165
  • GC03P033290

Summaries for FBXL2 Gene

Entrez Gene Summary for FBXL2 Gene

  • 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]

GeneCards Summary for FBXL2 Gene

FBXL2 (F-Box And Leucine Rich Repeat Protein 2) is a Protein Coding gene. Diseases associated with FBXL2 include Hepatitis C Virus. GO annotations related to this gene include ubiquitin-protein transferase activity and protein phosphatase binding. An important paralog of this gene is FBXL20.

UniProtKB/Swiss-Prot for FBXL2 Gene

  • Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity).

Gene Wiki entry for FBXL2 Gene

Additional gene information for FBXL2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FBXL2 Gene

Genomics for FBXL2 Gene

Regulatory Elements for FBXL2 Gene

Enhancers for FBXL2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH03H033437 1.4 ENCODE dbSUPER 20.5 +162.9 162912 5 HDGF PKNOX1 FOXA2 ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 CNOT10 PDCD6IP UBP1 FBXL2 GLB1 TMPPE CMTM6 PIR40256 GC03M033417
GH03H033425 1.3 Ensembl ENCODE dbSUPER 20.7 +151.1 151108 5 KLF1 FEZF1 ZNF384 ZIC2 BCL11B ZFHX2 ZNF316 GLI2 ZBTB20 EGR2 FBXL2 UBP1 GC03M033417 PIR40256
GH03H033372 1.1 Ensembl ENCODE 22.4 +95.9 95874 0 CTCF PKNOX1 ATF1 RB1 TBL1XR1 JUN ZNF2 RAD21 FOSL1 CC2D1A FBXL2 RNU7-110P
GH03H033577 1.4 FANTOM5 Ensembl ENCODE 15.1 +301.5 301544 2 SOX13 FOXA2 JUN CEBPG TEAD3 ZNF316 POLR2A FOS HOMEZ MAFK FBXL2 CLASP2 UBP1 COX6CP10 GC03M033644
GH03H033355 1 Ensembl ENCODE 20.9 +78.8 78801 1 HDAC1 PKNOX1 ATF1 ARNT CEBPG MTA3 SCRT2 SOX6 SMARCA4 HDAC2 FBXL2 SUSD5 UBP1 RNU7-110P
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around FBXL2 on UCSC Golden Path with GeneCards custom track

Promoters for FBXL2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000150623 776 1600 PKNOX1 ATF1 RB1 FUS ARID4B SIN3A BMI1 EGR1 ATF7 CREM

Genomic Location for FBXL2 Gene

Chromosome:
3
Start:
33,277,025 bp from pter
End:
33,403,662 bp from pter
Size:
126,638 bases
Orientation:
Plus strand

Genomic View for FBXL2 Gene

Genes around FBXL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FBXL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FBXL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FBXL2 Gene

Proteins for FBXL2 Gene

  • Protein details for FBXL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UKC9-FBXL2_HUMAN
    Recommended name:
    F-box/LRR-repeat protein 2
    Protein Accession:
    Q9UKC9
    Secondary Accessions:
    • B4DQV0
    • E9PD06
    • Q6IAN3
    • Q9NVQ8
    • Q9UK27
    • Q9UKA5
    • Q9Y3Y9

    Protein attributes for FBXL2 Gene

    Size:
    423 amino acids
    Molecular mass:
    47062 Da
    Quaternary structure:
    • Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2 (PubMed:10531037). Interacts with PCYT1A. Interacts with calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2) (By similarity). Interacts with CCND2 and CCND3 (PubMed:22323446, PubMed:22020328). Interacts with PIK3R2; PIK3R2 is a substrate ubiquitinated by the SCF(FBXL2) complex (PubMed:23604317). May interact with PIK3R1 (PubMed:23604317). Interacts with PTPN13. Interacts with hepatitis C virus non-structural protein 5A (NS5A) and less efficiently, with hepatitis C virus non-structural protein 5B (NS5B); a reaction crucial for hepatitis C virus RNA replication (PubMed:15893726).
    Miscellaneous:
    • Deletion of the F-box domain creates a dominant-negative protein that inhibits replication of hepatitis C virus RNA when overexpressed in a hepatoma cell line; this inhibition could be overcome by NS5A coexpression.
    SequenceCaution:
    • Sequence=AAF03128.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Alternative splice isoforms for FBXL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FBXL2 Gene

Post-translational modifications for FBXL2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for FBXL2 Gene

Domains & Families for FBXL2 Gene

Gene Families for FBXL2 Gene

Protein Domains for FBXL2 Gene

Graphical View of Domain Structure for InterPro Entry

Q9UKC9

UniProtKB/Swiss-Prot:

FBXL2_HUMAN :
  • The CAAX motif is a signal for the geranylgeranylation of FBXL2 and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex.
Domain:
  • The CAAX motif is a signal for the geranylgeranylation of FBXL2 and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex.
genes like me logo Genes that share domains with FBXL2: view

Function for FBXL2 Gene

Molecular function for FBXL2 Gene

UniProtKB/Swiss-Prot Function:
Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity).

Gene Ontology (GO) - Molecular Function for FBXL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 contributes_to ubiquitin-protein transferase activity IDA 23604317
GO:0005515 protein binding IPI 15893726
GO:0005516 calmodulin binding IEA --
GO:0019903 protein phosphatase binding IPI 23604317
GO:0036312 phosphatidylinositol 3-kinase regulatory subunit binding IPI 23604317
genes like me logo Genes that share ontologies with FBXL2: view
genes like me logo Genes that share phenotypes with FBXL2: view

Animal Model Products

CRISPR Products

miRNA for FBXL2 Gene

miRTarBase miRNAs that target FBXL2

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for FBXL2
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for FBXL2 Gene

Localization for FBXL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FBXL2 Gene

Membrane; Lipid-anchor.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FBXL2 gene
Compartment Confidence
extracellular 2
cytosol 2
peroxisome 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Nucleoli (2)
  • Nucleus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FBXL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm TAS 10508920
GO:0016020 membrane IEA,IDA 15893726
GO:0019005 SCF ubiquitin ligase complex IDA 23604317
genes like me logo Genes that share ontologies with FBXL2: view

Pathways & Interactions for FBXL2 Gene

SuperPathways for FBXL2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for FBXL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006464 cellular protein modification process TAS 10531035
GO:0006508 proteolysis TAS 10531035
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0006513 protein monoubiquitination IEA --
GO:0010506 regulation of autophagy IMP 23604317
genes like me logo Genes that share ontologies with FBXL2: view

No data available for Pathways by source and SIGNOR curated interactions for FBXL2 Gene

Drugs & Compounds for FBXL2 Gene

No Compound Related Data Available

Transcripts for FBXL2 Gene

Unigene Clusters for FBXL2 Gene

F-box and leucine-rich repeat protein 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for FBXL2
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

Alternative Splicing Database (ASD) splice patterns (SP) for FBXL2 Gene

No ASD Table

Relevant External Links for FBXL2 Gene

GeneLoc Exon Structure for
FBXL2
ECgene alternative splicing isoforms for
FBXL2

Expression for FBXL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FBXL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FBXL2 Gene

This gene is overexpressed in Brain - Cortex (x4.1) and Brain - Frontal Cortex (BA9) (x4.0).

Protein differential expression in normal tissues from HIPED for FBXL2 Gene

This gene is overexpressed in Retina (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for FBXL2 Gene



Protein tissue co-expression partners for FBXL2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of FBXL2 Gene:

FBXL2

SOURCE GeneReport for Unigene cluster for FBXL2 Gene:

Hs.475872

mRNA Expression by UniProt/SwissProt for FBXL2 Gene:

Q9UKC9-FBXL2_HUMAN
Tissue specificity: Expressed in brain, heart, kidney, liver, lung, pancreas and placenta.

Evidence on tissue expression from TISSUES for FBXL2 Gene

  • Nervous system(4.8)
genes like me logo Genes that share expression patterns with FBXL2: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for FBXL2 Gene

Orthologs for FBXL2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for FBXL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia FBXL2 33 34
  • 100 (n)
dog
(Canis familiaris)
Mammalia FBXL2 33 34
  • 93.84 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia FBXL2 34
  • 90 (a)
OneToOne
cow
(Bos Taurus)
Mammalia FBXL2 33 34
  • 88.81 (n)
mouse
(Mus musculus)
Mammalia Fbxl2 33 16 34
  • 87.94 (n)
rat
(Rattus norvegicus)
Mammalia Fbxl2 33
  • 87.39 (n)
chicken
(Gallus gallus)
Aves FBXL2 33 34
  • 80.33 (n)
lizard
(Anolis carolinensis)
Reptilia FBXL2 34
  • 76 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii fbxl2 33 34
  • 74.41 (n)
sbcb783 33
fruit fly
(Drosophila melanogaster)
Insecta CG9003 35 34
  • 55 (a)
worm
(Caenorhabditis elegans)
Secernentea C02F5.7a 35
  • 49 (a)
C02F5.7b 35
  • 48 (a)
C02F5.7 34
  • 44 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 49 (a)
OneToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU06250 33
  • 41.92 (n)
Species where no ortholog for FBXL2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for FBXL2 Gene

ENSEMBL:
Gene Tree for FBXL2 (if available)
TreeFam:
Gene Tree for FBXL2 (if available)

Paralogs for FBXL2 Gene

Paralogs for FBXL2 Gene

genes like me logo Genes that share paralogs with FBXL2: view

Variants for FBXL2 Gene

Sequence variations from dbSNP and Humsavar for FBXL2 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
VAR_036071 A colorectal cancer sample
rs1000010952 -- 33,294,394(+) GCCTG(A/G)CCCCA intron-variant
rs1000021124 -- 33,287,815(+) CAGTG(C/T)CTGGC intron-variant, upstream-variant-2KB
rs1000042094 -- 33,404,450(+) AATGA(A/G)GACTC intron-variant, nc-transcript-variant, downstream-variant-500B
rs1000069396 -- 33,317,054(+) ATGCT(A/G)TCACG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for FBXL2 Gene

Variant ID Type Subtype PubMed ID
esv2759138 CNV gain 17122850
esv3595794 CNV loss 21293372
nsv1001132 CNV gain 25217958
nsv10258 CNV loss 18304495
nsv1139102 CNV deletion 24896259
nsv477267 CNV novel sequence insertion 20440878
nsv522292 CNV loss 19592680
nsv525895 CNV gain 19592680
nsv822052 CNV loss 20364138
nsv834653 CNV loss 17160897

Variation tolerance for FBXL2 Gene

Residual Variation Intolerance Score: 17.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.98; 20.16% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for FBXL2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
FBXL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FBXL2 Gene

Disorders for FBXL2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for FBXL2 Gene - From: GeneCards

Disorder Aliases PubMed IDs
hepatitis c virus
  • hepatitis c virus, response to therapy of
- elite association - COSMIC cancer census association via MalaCards
Search FBXL2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for FBXL2

Genetic Association Database (GAD)
FBXL2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FBXL2
genes like me logo Genes that share disorders with FBXL2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for FBXL2 Gene

Publications for FBXL2 Gene

  1. Identification of a family of human F-box proteins. (PMID: 10531035) Cenciarelli C … Pagano M (Current biology : CB 1999) 2 3 4 60
  2. FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade. (PMID: 23604317) Kuchay S … Pagano M (Nature cell biology 2013) 3 4 60
  3. F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. (PMID: 22323446) Chen BB … Mallampalli RK (Blood 2012) 3 4 60
  4. F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest. (PMID: 22020328) Chen BB … Mallampalli RK (Oncogene 2012) 3 4 60
  5. Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication. (PMID: 15893726) Wang C … Ye J (Molecular cell 2005) 3 4 60

Products for FBXL2 Gene

Sources for FBXL2 Gene

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