METTL3 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 hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing. In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing. M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation. In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs. M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop. M6A also regulates circadian regulation of hepatic lipid metabolism. M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis. Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites. M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation. Inhibits the type I interferon response by mediating m6A methylation of IFNB. M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist. M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells. METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8. Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm. Its overexpression in a number of cancer cells suggests that it may participate to cancer cell proliferation by promoting mRNA translation. Belongs to the MT-A70-like family. Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Methyltransferase; RNA processing
Chromosomal Location of human Ortholog: 14q11.2
Cellular Component:  cytoplasm; nuclear speck; nucleoplasm; nucleus; RNA N6-methyladenosine methyltransferase complex
Molecular Function:  methyltransferase activity; mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity; mRNA (N6-adenosine)-methyltransferase activity; mRNA binding; protein binding; protein heterodimerization activity; RNA methyltransferase activity; S-adenosyl-L-methionine binding
Biological Process:  adenosine to inosine editing; cellular response to DNA damage stimulus; cellular response to UV; circadian rhythm; dosage compensation by inactivation of X chromosome; endothelial to hematopoietic transition; forebrain radial glial cell differentiation; gliogenesis; innate immune response; mRNA catabolic process; mRNA destabilization; mRNA methylation; mRNA processing; mRNA splicing, via spliceosome; negative regulation of Notch signaling pathway; negative regulation of type I interferon-mediated signaling pathway; oogenesis; positive regulation of cap-independent translational initiation; positive regulation of translation; primary miRNA processing; regulation of hematopoietic stem cell differentiation; regulation of meiotic cell cycle; regulation of T cell differentiation; RNA methylation; spermatogenesis; stem cell population maintenance
Reference #:  Q86U44 (UniProtKB)
Alt. Names/Synonyms: adoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase; hMETTL3; IME4; M6A; methyltransferase like 3; Methyltransferase-like protein 3; METTL3; MGC4336; mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase; mRNA m(6)A methyltransferase; MT-A70; MTA70; N6-adenosine-methyltransferase 70 kDa subunit; N6-adenosine-methyltransferase catalytic subunit; Spo8
Gene Symbols: METTL3
Molecular weight: 64,474 Da
Basal Isoelectric point: 5.98  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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