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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
Location 12q24.21      Physical location : 117.348.760 - 117.468.953
Synonym name
  • F-box only protein 29
  • F-box and WD-40 domain-containing protein 8
  • Synonym symbol(s) FBX29, FBXO29, FBW8, FBW6, FBXW6
    DNA
    TYPE functioning gene
    STRUCTURE 120.19 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    SDS-RS1 12q24.21 serine dehydratase related sequence 1 LHX5 12q24.31-q24.32 LIM homeobox protein 5 KIAA0682 12q23.3-q24.2 LIM homeobox protein 5 TBX5 12q24.1 T-box 5 LOC387886 12 LOC387886 LOC390361 12 similar to microtubule-associated proteins 1A/1B light chain 3 LOC386654 12q24.1-q24.2 OSTF1 pseudogene TBX3 12q24.1 T-box 3 (ulnar mammary syndrome) LOC387887 12 LOC387887 KIAA1025 LOC387888 12 LOC387888 FLJ21415 12q24.22 hypothetical protein FLJ21415 FLJ14627 12q24.22-q24.23 hypothetical protein FLJ14627 HRK 12q24.23 harakiri, BCL2 interacting protein (contains only BH3 domain) FBXW8 12q24.21 F-box and WD-40 domain protein 8 TSC 12q24.23 hypothetical protein FLJ20607 FBXO21 12q24.21 F-box only protein 21 NOS1 12q24.2-q24.31 nitric oxide synthase 1 (neuronal) KSR2 12q24.23 kinase suppressor of Ras-2 RFC5 12q24.2-q24.3 replication factor C (activator 1) 5, 36.5kDa WSB2 12q24.23 WD repeat and SOCS box containing protein 2 FLJ20674 12q24.23 hypothetical protein FLJ20674 PBP 12q24.23 prostatic binding protein JIK 12q24.2 prostatic binding protein SDS3 12q24.23 likely ortholog of mouse Sds3 LOC144747 12q24.23 hypothetical protein LOC144747 H11 LOC387889 12 hypothetical gene supported by U41745; NM_014891 MGC39827 12q24.23 hypothetical protein MGC39827 LOC387890 12 similar to hypothetical protein C130069F04 PRKAB1 12q24.1-q24.3 protein kinase, AMP-activated, beta 1 non-catalytic subunit CIT 12q24.2 citron (rho-interacting, serine/threonine kinase 21) LOC92558 12q24.31 hypothetical protein LOC92558 RAB35 12q24.31 RAB35, member RAS oncogene family GCN1L1 12q24.3 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) RPLP0 12q24.2 ribosomal protein, large, P0 PXN 12q24 paxillin FLJ23042 12q24.31 hypothetical protein FLJ23042 LOC283458 12q24.31 nucleoside diphosphate kinase B-like pseudogene
    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