Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MFN2 contributors: mct/ - updated : 08-04-2014
HGNC name mitofusin 2
HGNC id 16877
Corresponding disease
CMT2A2 Charcot-Marie-Tooth disease, axonal, type 2A2
HMSN6 hereditary motor and sensory neuropathy VI
Location 1p36.22      Physical location : 12.040.237 - 12.073.571
Synonym name
  • mitochondrial fusion gene
  • mitochondrial assembly regulatory factor
  • transmembrane GTPase MFN2
  • hyperplasia suppressor
  • Synonym symbol(s) CPRP1, KIAA0214, MARF, HSG
    EC.number 3.6.5.-
    DNA
    TYPE functioning gene
    STRUCTURE 33.34 kb     19 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • TP53 binding site in the promoter
  • TATA-less promoter contains a CpG island, and proximal MFN2 promoter contains six putative Sp1 motifs (Sp1 binds to the MFN2 promoter and its overexpression activates the MFN2 promoter in vascular smooth muscle cells) (
  • MAPPING cloned Y linked N status provisional
    Physical map
    FRAP1 1p36.3-p36.2 FK506 binding protein 12-rapamycin associated protein 1 CDT6 1p36.3-p36.2 angiopoietin-like factor TERE1 1p36 angiopoietin-like factor KIAA1337 1p36.21 KIAA1337 protein FBXO2 1p36.21 F-box only protein 2 FBX30 1p36.21 F-box protein FBX30 FBXO6 1p36.23-p36.11 F-box only protein 6 MAD2L2 1p36 MAD2 mitotic arrest deficient-like 2 (yeast) LOC374946 1p36.21 hypothetical gene supported by AK075558; BC021286 AGTRAP 1p36.21 angiotensin II receptor-associated protein DKFZp434E1410 1p36.21 hypothetical protein DKFZp434E1410 MTHFR 1p36.3 5,10-methylenetetrahydrofolate reductase (NADPH) CLCN6 1p36.2 chloride channel 6 NPPA 1p36.2 natriuretic peptide precursor A NPPB 1p36.2 natriuretic peptide precursor B LOC390997 1 similar to SET binding factor 1 isoform a; myotubularin-related protein 5 MGC33867 1p36.21 hypothetical protein MGC33867 PLOD 1p36.31 procollagen-lysine, 2-oxoglutarate 5-dioxygenase (lysine hydroxylase, Ehlers-Danlos syndrome type VI) MFN2 1p36.21 mitofusin 2 FLJ12438 1p36.21 hypothetical protein FLJ12438 TNFRSF8 1p36 tumor necrosis factor receptor superfamily, member 8 TNFRSF1B 1p36.32 tumor necrosis factor receptor superfamily, member 1B LOC390998 1 similar to 60S ribosomal protein L10 (QM protein) (Tumor suppressor QM) (Laminin receptor homolog) FLJ10619 DHRS3 1p36.1 dehydrogenase/reductase (SDR family) member 3 LOC343066 1p36.21 similar to Arylacetamide deacetylase (AADAC) LOC126767 1p36.21 similar to arylacetamide deacetylase MGC35194 1p36.21 hypothetical protein MGC35194 LOC390999 1 similar to Hypothetical protein DJ1198H6.2 LOC65121 1p36.21 hypothetical protein similar to preferentially expressed antigen of melanoma
    RNA
    TRANSCRIPTS type messenger
    text two transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 4540 - 757 - 2010 20335458
    19 - 4685 - 757 - 2010 20335458
    - - - - - localized in mitochondria but did not alter mitochondrial morphology in cells or in skeletal muscle fibers 2013 23941871
  • lacking the two transmembrane domains and the C-terminal coiled coil
  • activated basal and maximal respiration both in muscle and liver cells
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   lowly
    Nervousbrain   lowly
    Reproductivemale systemtestis   
    Urinarykidney   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines myeloid
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • both the N-terminal (AA1-264) and the C-terminal (aa 265-757) fragments of MFN2 blocked cell proliferation through distinct mechanisms
  • a ATP/GTP binding site motif
  • a transmembrane domain
  • two coiled-coil regions
  • a HR1 domain
  • C-terminal fragment of MFN2 inhibited cell proliferation by interacting with RAS
  • conjugated ubiquitinated
    HOMOLOGY
    interspecies ortholog to murine Mfn2
    ortholog to rattus mfn2
    Homologene
    FAMILY
  • mitofusin family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • anchored at the outer mitochondrial membrane and mediates fusion of the outer membrane
  • located on both mitochondria and ER
  • basic FUNCTION
  • may play a role in the pathophysiology of obesity
  • regulating the mitochondrial network architecture by fusion of mitochondria required to maintain the functional peripheral nerve axon
  • involved in mitochondrial biogenesis, mediating intermitochondrial adhesion and retraction from the cell periphery and accumulation in the perinuclear region, and playing a role in mitochondrial fusion, required for proper mitochondrial distribution and outgrowth of dendritic spines in Purkinje cells
  • required for postnatal development of the cerebellum (Purkinje cells require MFN2 for dendritic outgrowth, spine formation, and cell survival)
  • having a signaling role in the regulation of apoptosis that extends beyond its role in mitochondrial fusion
  • regulating the mitochondrial fusion with MFN1 and OPA1
  • key components in mitochondrial membrane fusion and division
  • dynamin-like GTPase required for mitochondrial fusion
  • tethers ER to mitochondria, a juxtaposition required for efficient mitochondrial Ca(2+) uptake
  • acts as an inhibitor of antiviral signaling, a function that may be distinct from its role in mitochondrial dynamics
  • tethering the endoplasmic reticulum and mitochondria to control the efficiency of mitochondrial uptake of Ca2+ ions
  • has lower GTPase activity and is thought to stabilize the interactions between mitochondria
  • regulates shape of the ER and tethers it to mitochondria, by engaging in homo- and hetero-complexes comprising MFN2 at the ER and MFN2 or MFN1 on mitochondria
  • role for mitofusins in directly regulating mitochondrial transport and offer important insight into the cell type specificity and molecular mechanisms of axonal degeneration in CMT2A and dominant optic atrophy
  • suppressor of cell proliferation that may also exert apoptotic effects via the mitochondrial apoptotic pathway
  • ubiquitination of MFN1 and MFN2 play a role in PINK1/PARK2-mediated mitophagy
  • dynamin-like protein that is involved in the rearrangement of the outer mitochondrial membrane
  • mediator of mitochondrial fusion, an evolutionarily conserved process responsible for the surveillance of mitochondrial homeostasis
  • in cardiac myocytes, controls mitochondrial morphogenesis and serves to predispose cells to mitochondrial permeability transition and to trigger cell death
  • important component in the mechanism whereby mitochondrial depolarization inhibits CRAC (Ca2+ release-activated Ca2+ channel) activity
  • mitochondrial MFN2 is involved in regulating store-operated calcium entry after mitochondrial depolarization
  • might serve as a brake, inhibiting Ca2+ entry only after mitochondria depolarize
  • MFN1 and MFN2 function to maintain mitochondrial networks by binding one another and initiating outer mitochondrial membrane fusion
  • mitochondrial dynamics, particularly those mediated by the mitofusins, play a role in endothelial cell function and viability
  • unique unexpected role of MFN2 coordinating mitochondria and endoplasmic reticulum function, leading to modulation of insulin signaling and glucose homeostasis
  • is an ER stress-inducible factor that contributes to ER homeostasis
  • MFN2 but not MFN1 is an ER stress-inducible protein that is required for the proper temporal sequence of the ER stress response
  • is an ER stress-inducible protein that is required for the adaptation of the ER to stress
  • serves as a major determinant of cardiomyocyte apoptosis mediated by oxidative stress
  • novel and essential role of MFN2 in mediating cardiac autophagy
  • does not play a critical role in the juxtapostion of ER and mitochondria
  • MFN1, MFN2, PARK2 regulating mitochondrial spheroid formation and mitophagy that could represent different strategies of mitochondrial homeostatic response to oxidative stress
  • participates in mitochondrial fusion, is required to maintain normal mitochondrial metabolism in skeletal muscle and liver
  • crucial involvement in mediating ER stress-induced leptin resistance
  • mitochondria and melanosomes establish physical contacts modulated by MFN2 and involved in organelle biogenesis
  • mitochondrial fusion protein that is critical for mitochondrial DNA integrity and function
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms homomultimers and heteromultimers with MFN1 and STOML2 (large hetero-oligomeric complex with STOML2)
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP/GTP binding
  • protein
  • interacting with DNM1L and MARCH5
  • interact with mammalian Miro (RHOT1/RHOT2) and Milton (TRAK1/TRAK2) proteins, members of the molecular complex that links mitochondria to kinesin motors
  • TP53-inducible target gene (positive correlation exists between MFN2 and TP53 expression)
  • TCHP interacting with MFN2 to regulate mitochondrial morphology and tethering with the ER
  • MARCH5 interacts with and ubiquitinates mitochondrial MFN2, but not ER-associated MFN2 (specific interaction between MARCH5 C-terminal domain and MFN2 HR1 domain)
  • is required for the full activation of the NLRP3 inflammasomes in macrophages
  • AMFR localizes to mitochondria-associated ER and targets the mitofusin (MFN1 and MFN2) mitochondrial fusion proteins for degradation
  • inactive cytoplasmic SMAD2 rapidly promotes mitochondrial fusion by recruiting RIN1 into a complex with MFN2
  • cell & other
    REGULATION
    induced by myogenesis
    Other ubiquitin proteasome system (UPS) is involved in MFN1, MFN2 degradation
    ubiquitinated in a PINK1/PARK2-dependent manner upon induction of mitophagy
    ASSOCIATED DISORDERS
    corresponding disease(s) CMT2A2 , HMSN6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    (transversion or transition) in some patients with Charcot-Marie-Tooth disease type 2A
    constitutional     --other  
    dysregulation of MFN2 expression in obesity or type 2 diabetes (collaboration with TNFalpha and interleukin-6 )
    constitutional     --over  
    by body weight loss in skeletal muscle of obese humans
    constitutional     --low  
    by type 2 diabetes in skeletal muscle
    constitutional     --over  
    drastically changes mitochondrial morphology, forming mitochondrial clusters and causes mitochondrial dysfunction and cell death
    constitutional     --low  
    found in Huntington disease patients relative to the controls
    constitutional     --low  
    loss of MFN2 might therefore be expected to increase the number of STIM1 multimers that successfully migrate to ER-PM junctions, resulting in increased Ca2+ entry
    constitutional     --low  
    in trophoblastic cells could be an important cause of early miscarriage
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyacquired 
    may serve as an accessible therapeutic target for the treatment of neuronal trauma and stroke
    immunologyimmunodeficiency 
    might be a novel therapeutic target in T cell apoptosis related disorders
    ANIMAL & CELL MODELS
  • Mfn-2-deficient mice display modest cardiac hypertrophy accompanied by slight functional deterioration
  • hearts from cardiac-specific MFN2 knock-out mice had abnormal mitochondrial and cellular metabolism and were vulnerable to ischemia-reperfusion challenge
  • ablation of mitochondrial fusion proteins Mfn1 and Mfn2 in the embryonic mouse heart arrested mouse heart development and impaired differentiation of ESCs into cardiomyocytes