Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:Q86U44 METTL3
| Class:Id | ReferenceGeneProduct:95685 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-580 added on Fri February 6 2015;initiator methionine:1 for 95685 removed on Fri Nov 03 2023;initiator methionine: for 95685 added on Fri Nov 03 2023;initiator methionine: for 95685 removed on Fri Aug 15 2025;initiator methionine:1 for 95685 added on Fri Aug 15 2025 |
| _displayName | UniProt:Q86U44 METTL3 |
| _timestamp | 2025-08-15 21:46:53 |
| chain | initiator methionine:1 chain:2-580 |
| checksum | 63A7F10195A3C6AC |
| comment | 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 hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27281194, PubMed:27373337, PubMed:27627798, PubMed:28297716, PubMed:29348140, PubMed:29506078, PubMed:30428350, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27281194, PubMed:27373337, PubMed:27627798). 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 (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). 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 (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). 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 (By similarity). M6A also regulates circadian regulation of hepatic lipid metabolism (PubMed:30428350). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Also required for oogenesis (By similarity). 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 (PubMed:28297716). 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 (By similarity). Inhibits the type I interferon response by mediating m6A methylation of IFNB (PubMed:30559377). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). 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 (PubMed:27602518). 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 (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). 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 (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation (PubMed:27117702). During human coronavirus SARS-CoV-2 infection, adds m6A modifications in SARS-CoV-2 RNA leading to decreased RIGI binding and subsequently dampening the sensing and activation of innate immune responses (PubMed:33961823).CATALYTIC ACTIVITY an adenosine in mRNA + S-adenosyl-L-methionine = an N(6)-methyladenosine in mRNA + S-adenosyl-L-homocysteine + H(+)ACTIVITY REGULATION Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (By similarity). Methyltransferase activity is inhibited by sumoylation (PubMed:29506078).SUBUNIT Heterodimer; heterodimerizes with METTL14 to form an antiparallel heterodimer that constitutes an active methyltransferase (PubMed:27281194, PubMed:27373337, PubMed:27627798). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:24407421, PubMed:24981863, PubMed:27602518, PubMed:29348140, PubMed:29506078, PubMed:29507755). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:24407421, PubMed:24981863, PubMed:27602518, PubMed:29507755). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:27602518, PubMed:29507755). Interacts with NCBP1/CBP80 (PubMed:27117702). Interacts with EIF4E (PubMed:27117702). Interacts with EIF3B (PubMed:27117702).INTERACTION Colocalizes with speckles in interphase nuclei, suggesting that it may be associated with nuclear pre-mRNA splicing components (PubMed:9409616). In response to ultraviolet irradiation, colocalizes to DNA damage sites however, it probably does not bind DNA but localizes in the vicinity of DNA damage sites (PubMed:28297716).ALTERNATIVE PRODUCTS Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.INDUCTION Overexpressed in a number of cancer tissues, such as lung adenocarcinoma and colon adenocarcinoma (PubMed:27117702).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.PTM Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1.SIMILARITY Belongs to the MT-A70-like family. |
| description | recommendedName: fullName evidence="30"N(6)-adenosine-methyltransferase catalytic subunit METTL3 ecNumber evidence="14 15 17 20 21 26"2.1.1.348 alternativeName: fullName evidence="30"Methyltransferase-like protein 3 shortName evidence="28"hMETTL3 alternativeName: N(6)-adenosine-methyltransferase 70 kDa subunit shortName: MT-A70 |
| geneName | METTL3 MTA70 |
| identifier | Q86U44 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Biological rhythms Cytoplasm Differentiation Direct protein sequencing DNA damage Immunity Innate immunity Isopeptide bond Methyltransferase Nucleus Oogenesis Phosphoprotein Proteomics identification Reference proteome RNA-binding S-adenosyl-L-methionine Spermatogenesis Transferase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | METTL3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8993162] ENSEMBL:ENSG00000165819 METTL3 [Homo sapiens] |
| secondaryIdentifier | MTA70_HUMAN O14736 Q86V05 Q9HB32 |
| sequenceLength | 580 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:150625] UniProt:Q86U44-2 METTL3 [Homo sapiens] [ReferenceIsoform:409810] UniProt:Q86U44-1 METTL3 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:72091] METTL3 [nucleoplasm] [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:Q86U44 METTL3 (95685)
