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FLASH GENE
Symbol METTL3 contributors: mct - updated : 05-11-2019
HGNC name methyltransferase like 3
HGNC id 17563
Location 14q11.2      Physical location : 21.966.282 - 21.979.457
Synonym name
  • Inducer of MEiosis 4
  • Synonym symbol(s) 2310024F18Rik, Spo8, M6A, IME4, MT-A70, hMETTL3, MGC4336
    EC.number 2.1.1.62/2.1.1.348
    DNA
    TYPE functioning gene
    STRUCTURE 13.20 kb     11 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1980 - 580 - 2019 30659266
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   lowly
     thymus   lowly
    Digestiveintestinesmall intestine  lowly
    Endocrinepancreas   lowly
    Reproductivefemale systemovary  lowly
     male systemprostate  lowly
     male systemtestis  lowly
    Respiratorylung   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    one MT-A70 domain
    HOMOLOGY
    Homologene
    FAMILY methyltransferase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,ribosome
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    text
  • METTL3 associates with ribosomes and promotes translation in the cytoplasm
  • METTL3/METTL14 is found in the nucleus where it is localized to nuclear speckles and the splicing regulator WTAP is required for this distinct nuclear localization pattern
  • basic FUNCTION
  • methylates adenosine residues of some mRNAs
  • may play a role in the efficiencey of mRNA splicing, transport or translation
  • is sufficient to elicit circadian period elongation and RNA processing delay
  • is an RNA methyltransferase implicated in mRNA biogenesis, decay, and translation control through N(6)-methyladenosine (m(6)A) modification
  • important role of METTL3 in promoting translation of oncogenes in human lung cancer
  • METTL3 is the catalytically active subunit, while METTL14 plays a structural role critical for substrate recognition
  • METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding
  • controls myeloid differentiation of normal hematopoietic and leukemia cells
  • critical role of METTL3-mediated N6-methyladenosine (m6A) in regulating the development of mammalian cerebellum
  • new role for METTL3-mediated N6-methyladenosine (m6A) modification in increasing translation of certain immune transcripts for physiological promotion of dendritic cell (DC) activation and DC-based T cell response
  • RNA N6-methyladenosine methylase METTL3 inhibits hepatic insulin sensitivity via N6-methylation of FASN mRNA and promoting fatty acid metabolism
  • required for the epithelial-mesenchymal transition (EMT) process in vitro and for metastasis in vivo
  • crucial regulator in the progression of osteogenic differentiation
  • functional importance of METTL3 in osteogenic differentiation
  • CELLULAR PROCESS nucleotide, RNA splicing
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism nucleic
    signaling
    METTL3/ZMYM1/CDH1 signaling is a potential therapeutic target in anti-metastatic strategy against gastric cancer
    a component
  • RNA methyltransferase complex of WTAP, METTL3, and METTL14 regulates mitotic clonal expansion in adipogenesis
  • trimer N-6-methyltransferase METTL3-METTL14-WTAP complex is linked to such critical biological processes as cell differentiation, proliferation, and death
  • METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
  • INTERACTION
    DNA
    RNA binding
    small molecule
    protein
  • WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic activity of the m6A methyltransferase
  • METTL3 enhances mRNA translation through an interaction with the translation initiation machinery
  • METTL3 is required for MYOD1 mRNA expression in proliferative myoblasts
  • METTL3 promoted the expression of LAMTOR5 through N6-methyladenosine (m6A) modification
  • METTL3 regulates osteogenic differentiation and alternative splicing of VEGFA in bone marrow mesenchymal stem cells
  • BCL2 acted as the target of METTL3, thereby regulating the proliferation and apoptosis of breast cancer
  • ZMYM1 is a bona fide N6-methyladenosine (m6A) target of METTL3
  • METTL3 positively regulates expression of MYD88, a critical upstream regulator of NFKB1 signaling, by facilitating m6A methylation modification to MYD88-RNA
  • METTL3 can trigger growth of cervical cancer cells via upregulation of RAB2B
  • cell & other
    REGULATION
    Other important mechanism for SUMOylation of METTL3 regulating its N6-methyladenosine (m6A) RNA methyltransferase activity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    significantly augments calcium deposition and enhances alkaline phosphatase activity of mesenchymal stem cells, uncovering an inhibitory role of METTL3 in osteogenesis
    tumoral       gain of function
    in gastric cancer
    constitutional   deletion    
    of METTL3 from the adult haematopoietic system led to an accumulation of Haematopoietic stem cells (HSCs) in the bone marrow and a marked reduction of reconstitution potential due to a blockage of HSC differentiation
    constitutional        
    silencing METTL3 could sustain long-chain fatty acids (LCFAs) absorption through blocking the TRAF6-dependent inflammation response
    tumoral     --over  
    in lung adenocarcinoma
    tumoral     --low  
    of METTL3 and METTL14 expressions in childhood ETV6/RUNX1-positive acute lymphoblastic leukemia
    tumoral     --over  
    in cervical tumor tissues
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • elevated METTL3 level was predictive of poor prognosis in gastric cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    METTL3 might be a potential target for cervical cancer therapy
    ANIMAL & CELL MODELS
  • Mettl3 overexpression in MSCs protects the mice from estrogen deficiency-induced osteoporosis