UniProt ID: F1R777
FUNCTION: The METTL3-METTL14 heterodimer forms a N6- methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and haematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:28869969). In the heterodimer formed with mettl14, mettl3 constitutes the catalytic core (By similarity). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing and translation efficiency (By similarity). M6A is also involved in haematopoietic stem cells specification: m6A methylation and subsequent destabilization of mRNAs, such as notch1a, leads to decreased Notch dignaling, promoting endothelial to haematopoietic transition (PubMed:28869969). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (By similarity). Mediates methylation of pri-miRNAs (By similarity). {ECO:0000250|UniProtKB:Q86U44, ECO:0000250|UniProtKB:Q8C3P7, ECO:0000269|PubMed:28869969}.
CATALYTIC ACTIVITY: Reaction=adenosine in mRNA + S-adenosyl-L-methionine = H(+) + N(6)-methyladenosine in mRNA + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:55584, Rhea:RHEA-COMP:12414, Rhea:RHEA- COMP:12417, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:74411, ChEBI:CHEBI:74449; EC=2.1.1.348; Evidence={ECO:0000250|UniProtKB:Q86U44, ECO:0000250|UniProtKB:Q8C3P7};
SUBUNIT: Heterodimer; heterodimerizes with mettl14 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6- methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of mettl3 and mettl14. {ECO:0000250|UniProtKB:Q86U44}.
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86U44}. Nucleus speckle {ECO:0000250|UniProtKB:Q86U44}. Cytoplasm {ECO:0000250|UniProtKB:Q86U44}. Note=Colocalizes with speckles in interphase nuclei. Suggesting that it may be associated with nuclear pre-mRNA splicing components. {ECO:0000250|UniProtKB:Q86U44}.
TISSUE SPECIFICITY: Expressed in the haemato-vascular system: enriched in sorted endothelial cells and haemogenic endothelium (PubMed:28869969). {ECO:0000269|PubMed:28869969}.
DEVELOPMENTAL STAGE: Maternally expressed from the 4-cell stage and ubiquitously expressed through early embryogenesis, with enriched expression in the brain region at 36 hpf (hours post fertilization) (PubMed:24407421). {ECO:0000269|PubMed:24407421}.
DOMAIN: Gate loop 1 and gate loop 2 regions are adjacent to the S- adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction. {ECO:0000250|UniProtKB:Q86U44}.
DISRUPTION PHENOTYPE: Lethality 10 days post-fertilization (dpf) due to severe haematopoietic defects (PubMed:28869969). Levels of N6-methyladenosine (m6A)-containing mRNAs are significantly decreased and emergence of haematopoietic stem cells is blocked (PubMed:28869969). {ECO:0000269|PubMed:28869969}.
SIMILARITY: Belongs to the MT-A70-like family. {ECO:0000255|PROSITE-ProRule:PRU00489}.
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