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FLASH GENE
Symbol BTRC contributors: mct - updated : 24-04-2017
HGNC name beta-transducin repeat containing
HGNC id 1144
Location 10q24.32      Physical location : 103.113.824 - 103.317.068
Genatlas name F-box and WD40 domain protein 1A
Synonym name
  • F-box protein W1A
  • supernumerary limbs homolog
  • Synonym symbol(s) FWD1, FBW1A, BTRCP1, FBXW1A, BETATRCP, TRCP1, SLIMB, FWD-40, Scf
    DNA
    TYPE functioning gene
    STRUCTURE 203.51 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    PAX2 10q22.1-q24.3 paired box gene 2 C10orf6 10q24.31 chromosome 10 open reading frame 6 SEMA4G 10q24.2 sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4G MRPL43 10q24.1-q24.3 mitochondrial ribosomal protein L43 PEO1 KIAA1813 10q24 KIAA1813 protein FLJ23209 10q24.32 hypothetical protein FLJ23209 BA108L7.2 10q24.32 similar to rat tricarboxylate carrier-like protein FKSG28 10q24.32 hypothetical protein FKSG28 C10orf1 10q24 chromosome 10 open reading frame 1 TLX1 10q24 T-cell leukemia, homeobox 1 LBX1 10q24 transcription factor similar to D. melanogaster homeodomain protein lady bird late BTRC 10q24-q25 beta-transducin repeat containing POLL 10q23 polymerase (DNA directed), lambda DKFZP566F084 SHFM3 10q24 split hand/foot malformation (ectrodactyly) type 3 FGF8 10q24 fibroblast growth factor 8 (androgen-induced) NPM3 10q24.31 nucleophosmin/nucleoplasmin, 3 MGEA5 10q24.1-q24.3 meningioma expressed antigen 5 (hyaluronidase)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 splicing 6146 68.9 605 - 2011 21138764
    14 splicing 6013 64.8 569 - 2011 21138764
    lacking 108nt in the coding region compared to variant 1 36AA shorter isoform
    - - 6102 - 579 - 2011 21138764
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine   
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines gastric cancer cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    cell cycle     cell cycle, checkpoint, G1S
    Text widely
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • F-box near the N terminus
  • seven WD-40 repeats (beta transducin repeats) at the C terminus
  • conjugated FlavoP
    HOMOLOGY
    interspecies homolog to Xenopus btrcp1
    homolog to yeast S.cerevisiae met30
    homolog to Drosophila slimb
    homolog to murine Btrc
    homolog to Xenopus bTrCP1
    intraspecies homolog to FBXW11
    Homologene
    FAMILY F-box protein family,FBWS class/beta catenin ubiquitin ligase complex
    CATEGORY adaptor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • interacting with HIV1 Vpu to trigger the destruction of CD4 in the endoplasmic reticulum
  • functioning in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway,specific determinant for the signal-induced ubiquitination of I kappa B (NFKBIA)
  • ubiquitin conjugating enzyme and substrate recognition subunit of SCF ubiquitin protein ligase complex
  • specificity determinant for the signal-induced ubiquitanation of CHUK (IkappaB kinase-alpha)
  • HIV-1 Vpu protein interacts with CD4 within the endoplasmic reticula of infected cells and targets CD4 for degradation through interaction with BTRC
  • dispensable for the central clock in the suprachiasmatic nucleus
  • BTRC and FBXW11 were involved in the cell autonomous circadian rhythm generation in culture cells
  • potential role in regulating the eventual ratio of resulting differentiated retinal cell types
  • E3 ligase that targets various substrates essential for many aspects of tumorigenesis
  • may be an essential player in UVB induced responses in skin and can be a potential therapeutic target for skin cancer
  • is required for internalisation of the growth hormone receptor (GHR) and acts via a direct interaction with the ubiquitin-dependent endocytosis motif
  • controls GH receptor degradation via two different motifs, the UbE motif in the cytoplasmic tail of the GHR and a downstream degron, DSGRTS
  • directs the conjugation of ubiquitin to a variety of substrate proteins, leading to the destruction of the substrate by the proteasome
  • CELLULAR PROCESS protein, degradation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text ubiquitin-dependent protein degradation
    PATHWAY
    metabolism
    signaling signal transduction
    NFKB, WNT and hedgehog signaling pathway
    a component one of the four subunits of the E3 ubiquitin protein ligase complex:(SCF) with SKP1/CDC53,CUL1,RBX1,F-box protein (BTRC) bringing ubiquitin conjugating enzymes to substrates recruited by F-box
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HIV1Vpu (NFKBIA)
  • phosphorylated I kappa B alpha
  • pro-caspase-3 appears to be a substrate of SAG/ROC-SCF(BTRC) E3 Ub ligase, which protects cells from apoptosis through increased apoptosis threshold by reducing the basal level of pro-caspase-3
  • both BTRC and FBXW11 bind specifically to USP47, and point mutations in the TRCP WD-repeat region completely abolished USP47 binding, indicating an E3-substrate-type interaction
  • wild-type BMI1 but not the mutant BMI1 interacts with BTRC
  • interacting with PHLPP1 (cellular localization of BTRC is altered in glioblastoma, resulting in dysregulation of PHLPP1 and other substrates such as beta-catenin)
  • in the nucleus, BTRC promotes the degradation of NRF1 by catalyzing its polyubiquitination
  • both BTRC- and SYVN1-dependent degradation mechanisms regulate the transcriptional activity of NRF1 to maintain cellular homeostasis
  • BTRC regulates cell growth and autophagy by controlling the ubiquitination and destruction of DEPTOR, an endogenous mammalian target of rapamycin inhibitor, in a phosphorylation-dependent manner
  • E3 ligase subunit BTRC interacts with CTTN, and its overexpression reduced cortactin protein levels, an effect attenuated by MAPK1 inhibition
  • BTRC is a novel TERF1-associating protein
  • interacts directly via its WD40 domain with the UbE (ubiquitin-dependent endocytosis) motif in GHR, promoting GHR ubiquitination
  • BTRC-mediated regulation of OIP5 stability is a mechanism to restrict centromere function of OIP5 complex from late mitosis to early G1 phase
  • during the G2 phase of the cell division cycle, TFAP4 is targeted for proteasome-dependent degradation by the BTRC ubiquitin ligase
  • BHLHE40 is a highly unstable protein that is targeted for proteasome-dependent degradation by the BTRC ubiquitin ligase in cooperation with CSNK1A1
  • TRIB2 associated-BTRC, RFWD2 and SMURF1 reduced TCF4/CTNNB1 expression, and these effects could be enhanced by TRIB2
  • PPP1R15B is a BTRC substrate, and a Protein Phosphatase 1 (PP1) specificity subunit that targets the translation initiation factor EIF2S1 to promote the removal of a stress-induced inhibitory phosphorylation and increase cap-dependent translation
  • BTRC-mediated ubiquitination and degradation of liver-enriched transcription factor CREB3L3
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    of BTRC results in accumulation of MDM2 and decreased TP53 activity, and resistance to apoptosis induced by DNA damaging agents
    tumoral     --low  
    suppresses prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    combining BTRC inhibition with androgen ablation could benefit advanced prostate cancer patients
    ANIMAL & CELL MODELS