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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
Location 1p36.12      Physical location : 20.825.942 - 20.834.674
Synonym name
  • E3 ubiquitin ligase
  • ring finger protein 218
  • mitochondria-anchored protein ligase
  • growth inhibition and death E3 ligase
  • mitochondrial ubiquitin ligase activator of NF-kB 1
  • chromosome 1 open reading frame 166
  • Synonym symbol(s) GIDE, MAPL, MULAN, RNF218, C1orf166, FLJ12875, RP11-401M16.2
    EC.number 6.3.2.-/2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 8.73 kb     4 Exon(s)
    MAPPING cloned Y linked N status provisional
    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)
  • 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
    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
  • cell & other
    REGULATION
    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