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FLASH GENE
Symbol FBXL5 contributors: mct - updated : 21-08-2016
HGNC name F-box and leucine-rich repeat protein 5
HGNC id 13602
Location 4p15.32      Physical location : 15.606.006 - 15.657.035
Synonym name
  • F-box protein FBL5
  • p45SKP2-like protein
  • Synonym symbol(s) FBL4, FBL5, FLR1
    DNA
    TYPE functioning gene
    STRUCTURE 55.48 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3540 75.3 691 - 1999 10531035
    - splicing 1470 61.5 565 - 1999 10531035
    downstream start codon truncated
    11 - 3489 - 674 - 1999 10531035
    11 - 3537 - 690 - 1999 10531035
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrinepancreas   highly
     thyroid   highly
    Hearing/Equilibriumearinnercochlea highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, checkpoint, G1S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal hemerythrin (Hr)-like domain, characterized by a helical bundle held together by a di-iron center, that mediates its own differential stability by switching between two different conformations to communicate cellular iron availability
  • F-box 40 AA motif
  • five leucine-rich repeats (LRR) at the C terminus
  • HOMOLOGY
    Homologene
    FAMILY F-box protein family
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • located in the nucleus where it interacts with SNAI1 promoting its polyubiquitination and affecting Snail1 protein stability and function by impairing DNA binding
  • basic FUNCTION
  • phosphorylation dependent ubiquitination
  • substrate recognition subunit of SCF ubiquitin protein ligase complex
  • major role for FBXL5 in ensuring an appropriate supply of iron to cells
  • targets IREB2 for proteasomal degradation under iron- and oxygen-replete conditions, whereas itself is degraded when iron and oxygen availability decreases
  • role of FBXL5 in the maintenance of cellular and systemic iron homeostasis, suggesting a privileged role for the intestine in their regulation by virtue of its unique FBXL5 iron sensitivity
  • novel nuclear ubiquitin ligase controlling SNAI1 protein stability
  • regulates cellular and systemic iron homeostasis by facilitating IREB2 degradation
  • is essential for the maintenance of iron homeostasis and is a key sensor of bioavailable iron
  • undergoes constitutive ubiquitin-dependent degradation at the steady state
  • BTRC, FBXW7, FBXL14, FBXO45, FBXL5, FBXO11 play in controlling EMT during development and cancer progression, a process dependent on post-translational modifications that govern their interaction with target proteins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • FBXL5-IREB2 axis is integral to control of iron metabolism
  • a component
  • one of the four subunits of the E3 ubiquitin protein ligase complex :(SCF) with SKP1, CUL1, RBX1, F-box protein bringing ubiquitin conjugating enzymes to substrates recruited by F-box
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • various target proteins
  • interacts with DCTN1 and orchestrates its turnover via ubiquitination
  • under iron-replete conditions, FBXL5 recruits IREB2 to the SCF complex, where it is polyubiquitinated
  • is a novel SNAI1 ubiquitin ligase
  • interacts with and targets CTTN for ubiquitylation and subsequent proteasomal degradation (negative regulation of CTTN by FBXL5 in gastric cancer cells migration)
  • HERC2 is an FBXL5-associated protein (HERC2 regulates the basal turnover of FBXL5, and this ubiquitin-dependent degradation pathway contributes to the control of mammalian iron metabolism)
  • FBXL5 interacts with and targets NABP2 for ubiquitination and degradation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    is a novel, promising therapeutic target for lung cancers
    ANIMAL & CELL MODELS
  • Fbxl5-null mice die during embryogenesis, although viability is restored by simultaneous deletion of the Ireb2, but not Ireb1 gene