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FLASH GENE
Symbol TRIM63 contributors: mct - updated : 25-10-2013
HGNC name tripartite motif-containing 63
HGNC id 16007
DNA
TYPE functioning gene
STRUCTURE 16.32 kb     9 Exon(s)
regulatory sequence Binding site   transcription factor
text structure
  • promoter containing a near-perfect palindromic glucocorticoid response element (GRE) 200 base pairs upstream of the transcription start site (Waddell 2008)
  • MAPPING cloned Y linked N status confirmed
    Map pter - D1S234 - D1S2885 - TRIM63 - D1S455 - D1S2749 - cen
    Authors UCSC (2009)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1771 40.1 353 - -
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Nervousbrain    
    Respiratorylung    
    Visualeyeanterior segmentiris  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Muscularstriatumcardiac specific Homo sapiens
    Muscularstriatumskeletal specific Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text heart highly, all striated muscle tissues throughout development
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a ring finger motif in the N-terminus
  • a zing-binding type-2 B-box motif
  • a coiled-coil dimerization motif box in the central region (RBCQ) tripartite motif (TRIM)
  • a COS (C-terminal subgroup one signature) domain
  • conjugated MetalloP
    mono polymer homomer , heteromer , oligo
    HOMOLOGY
    interspecies homolog to rattus Trim63 (91.1 pc)
    homolog to murine Trim63 (92.6 pc)
    Homologene
    FAMILY
  • C-II TRIM family
  • C3HC4 RING finger subfamily
  • MURF subfamily
  • RBCC family
  • CATEGORY enzyme , regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,chromatin/chromosome
    text Z line and M line lattices of myofibrils
    basic FUNCTION
  • sarcomere-associated protein, involved in the cell cycle regulatory process of striated muscle cells
  • playing a role in striated muscle cell embryonic development
  • may coordinately regulate the energy metabolism of mitochondrial and cytoplasmic compartments
  • acting as an E3 ubiquitin ligase (Ozato 2008)
  • regulating proteasomal degradation of cardiac troponin I/TNNI3 and probably of other sarcomeric-associated proteins
  • may regulate the organization of myofibrils through TTN in muscle cells
  • involved in regulating muscle trophic homeostasis through interactions with a number of proteins including glycogen phosphorylase and FOXO (Forkhead box, subgroup O)
  • plays an important role in regulating cardiac size through alterations in protein turnover and that MuRF1 is not required to induce cardiac atrophy
  • muscle RING finger protein which is involved in muscle wasting
  • is involved in disuse-induced bone loss in both of the two major bone remodeling activities, osteoblastic bone formation and osteoclastic bone resorption
  • is responsible for mediating muscle atrophy that occurs during the period of active lung injury in humans, and skeletal muscle dysfunction persists despite resolution of lung injury
  • FBXO32 and TRIM63 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle
  • maintains muscle protein homeostasis by tagging the sarcomere proteins with ubiquitin for subsequent degradation by the ubiquitin-proteasome system (UPS)
  • CELLULAR PROCESS cell cycle
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • interacting with SUMO2, titin/TTN and GMEB1
  • interacting with TRIM54 and probably with TRIM55 and TNNI3
  • forming a ternary complex with GNB2L1 and PRKCE
  • binding to titin repeats, near the titin kinase domain, important for the stability of M-line region and thick filament structure
  • binding to ubiquitin (UBC9) conjugating enzyme 9 and isopeptidase
  • binding with glucocorticoid modulatory element binding protein-1 (GMEB1) suggesting that RNF28 may link myofibril signaling pathways and influences muscle gene expression
  • interacting with TNNI1, and TNNI2 (targeted for ubiquitylation and proteasome-depoendent degradation)
  • indirectly reduces MYBPC3 levels by regulating the transcription of myosin heavy chains (
  • FOXO3 and SMAD3, converge to coordinately and directly regulate transcription of TRIM63
  • cell & other
    REGULATION
    induced by FOXO1
    FOXO3
    Other developmentally regulated
    ASSOCIATED DISORDERS
    corresponding disease(s) CMH15
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    inhibition of TRIM63 could be a novel mechanism to prevent or reverse muscle wasting associated with various pathologies
    ANIMAL & CELL MODELS
  • murf1 knock out mice (Bodine 2001)
  • the increase in cardiac size in MuRF1 KO mice was related to a decrease in proteasome activity and an increase in Akt signaling relative to WT mice