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FLASH GENE
Symbol FBXW8 contributors: mct/pgu - updated : 17-04-2019
HGNC name F-box and WD-40 domain protein 8
HGNC id 13597
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 splicing 4673 - 532 - 1999 10531037
variant 2 lacks an in-frame codon in the 5' coding region, leading to an isoform missing an internal segment
11 splicing 4871 67 598 - 1999 10531037
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain    
Respiratorylung    
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 40AA F-box motif
  • five WD repeats
  • mono polymer complex
    HOMOLOGY
    Homologene
    FAMILY F-box protein family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • phosphorylating dependent ubiquination
  • mitotic regulator,inhibiting the anaphase promoting complex (cyclosome APC) and preventing mitotic exit in cytostatic factor (CSF) arrested eggs
  • plays an essential role in cancer cell proliferation through proteolysis of cyclin D1
  • OBSL1-regulated CUL7/FBXW8 ubiquitin signaling mechanism that orchestrates the morphogenesis of the Golgi apparatus and patterning of dendrites
  • in the absence of the CRTC2-mediated phosphorylation, FBXW8 is incapable of cytosolic translocation, thereby preventing degradation of cytosolic IRS1
  • CELLULAR PROCESS cell cycle, division, mitosis
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • putative component of a E3 ubiquitin protein ligase complex (SCF) with SKP1, CUL1, RBX1 bringing ubiquitin conjugating enzymes to substrates recruited by F-box
  • complexing with CUL7 (FBXW8-CUL7 complex plays a significant role in growth control)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TBC1D3 recruits F-box 8 (FBXW8), the substrate recognition domain of CUL7 E3 ligase
  • CRTC2 negatively feeds back to IRS1 via control of FBXW8 stability and localization
  • CRTC2 functions in the regulation of FBXW8 that allows FBXW8 to mediate IRS1 turnover following insulin stimulation
  • CUL7/FBXW8 ubiquitin ligase-mediated MAP4K1 degradation revealed a direct link and novel role of CUL7/FBXW8 ubiquitin ligase in the MAPK pathway, which plays a critical role in cell proliferation and differentiation
  • degradation of wildtype and mutant ATXN2 is dependent on FBXW8, and ATXN2 accumulation selectively modulates FBXW8 levels, while PARK2 might act indirectly through FBXW8
  • MRFAP1 is an interactor of the F-box protein FBXW8, and is degraded by means of the ubiquitin ligase CUL7/FBXW8 during mitotic anaphase-telophase transition and accumulated in mitotic metaphase
  • CUL7/FBXW8-mediated destruction of MRFAP1 is a regulatory component monitoring the anaphase-telophase transition and preventing genomic instability
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to breast cancer
    Variant & Polymorphism other
  • frameshift mutation, c.1312_1313delGT, associated with breast cancer
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS