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FLASH GENE
Symbol MUL1 contributors: SGE/npt - updated : 13-06-2019
HGNC name mitochondrial E3 ubiquitin ligase 1
HGNC id 25762
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 2474 - 352 - 2015 2624617
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveintestinelarge intestinecolon lowly
 liver    
Lymphoid/Immunethymus   lowly
Reproductivefemale systemplacenta   
Urinarykidney    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one RING-type zinc finger, required for E3 ligase activity
  • mono polymer homomer , oligo
    HOMOLOGY
    interspecies homolog to murine Mul1 (89.8pc)
    homolog to rattus Mul1 (90.1pc)
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    text
  • transported in mitochondrion-derived vesicles from the mitochondrion to the peroxisome
  • E3 ubiquitin ligase embedded in the outer mitochondrial membrane (OMM)
  • is a multifunctional E3 ubiquitin ligase anchored in the outer mitochondrial membrane with its RING finger domain facing the cytoplasm
  • basic FUNCTION
  • E3 ubiquitin-protein ligase that plays a role in the control of mitochondrial morphology
  • promotes mitochondrial fragmentation and influences mitochondrial localization (Braschi 2009)
  • inhibits cell growth (Zhang 2008)
  • upon overexpression, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis
  • have an important role in cell growth, cell death, and more recently in mitophagy
  • is an E3 ligase that regulates NFKB1 activation to protect cells from ER stress-induced apoptosis
  • E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria
  • MUL1 regulates metformin&
  • 8209;mediated AKT1 degradation and the antitumor effects of metformin in chemoresistant ovarian cancer cell lines
  • participates in various biological pathways involved in apoptosis, mitochondrial dynamics, and innate immune response
  • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ions Zn2+
  • protein
  • interacting with MAP3K7/TAK1
  • AKT1 was found to directly interact with MUL1 and to be ubiquitinated by MUL1
  • MUL1 E3 ubiquitin ligase is a specific substrate of HTRA2, and inactivation of HTRA2 protease leads to the deregulation of mitochondrial MUL1 E3 ubiquitin ligase and increased mitophagy
  • increase in MUL1 protein levels also fragments the mitochondria through the ubiquitination and subsequent proteasomal degradation of MFN2
  • MUL1 is a novel regulator of the DDX58-like receptor-dependent antiviral response, that otherwise functions to limit inflammation
  • MUL1 is involved in multiple biological pathways, and the interaction of GABARAP with MUL1-UBE2E3 supports the role of MUL1 as an important regulator of mitophagy and provides a plausible mechanism for its function in this process
  • MUL1, a mitochondria-localized E3 ligase, regulates selenite-induced mitophagy in an ATG5 and ULK1-dependent manner
  • specifically activated NFKB1 dependent gene expression in an E3 ligase activity-dependent manner
  • MUL1 appears to have some antagonistic functions to MARCH5 whereby MUL1 has a pro-mitophagy affect
  • in head and neck cancer (HNC) acts as negative regulator against AKT1
  • inactivation of MUL1 ligase leads to accumulation of UBXN7, with concomitant increase in HIF1A protein levels, reduction in oxidative phosphorylation, and increased glycolysis
  • cell & other
    REGULATION
    Other ubiquitination of UBXN7 targets the protein for proteasome degradation and inactivation of MUL1 leads to high levels of UBXN7 with concomitant increase in HIF1A protein
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in head and neck cancer (HNC)
    Susceptibility
  • to Parkinson disease (PD)
  • Variant & Polymorphism SNP
  • rs529974 in MUL1 gene was significantly associated with the risk of PD
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    regulation of FOXO3-MUL1-AKT1 axis can be a novel strategy for the treatment of head and neck cancer (HNC) with cisplatin (CDDP)
    cancerhead and neck 
    regulation of the MUL1-HSPA5 axis can be a novel strategy for the treatment of HNC
    ANIMAL & CELL MODELS