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mettl3

Gene
Mettl3
Protein
N6-adenosine-methyltransferase MT-A70-like protein
Organism
Drosophila melanogaster
Length
608 amino acids
Function
Catalytic component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of mRNAs, a modification that plays a role in the efficiency of mRNA splicing and is required for sex determination (PubMed:27919077, PubMed:27919081, PubMed:28675155). In the heterodimer formed with Mettl14, constitutes the catalytic core (By similarity). Required for sex determination and dosage compensation via Sxl alternative splicing: m6A methylation acts as a key regulator of Sxl pre-mRNA and promotes female-specific alternative splicing of Sxl, which determines female physiognomy (PubMed:27919077, PubMed:27919081, PubMed:28675155). M6A methylation is also required for neuronal functions (PubMed:27919077). During oogenesis, required for egg chamber development probably as part of the N/Notch signaling (PubMed:21873203).
Similarity
Belongs to the MT-A70-like family.
Mass
68.101 kDa
Sequence
MADAWDIKSLKTKRNTLREKLEKRKKERIEILSDIQEDLTNPKKELVEADLEVQKEVLQALSSCSLALPIVSTQVVEKIAGSSLEMVNFILGKLANQGAIVIRNVTIGTEAGCEIISVQPKELKEILEDTNDTCQQKEEEAKRKLEVDDVDQPQEKTIKLESTVARKESTSLDAPDDIMMLLSMPSTREKQSKQVGEEILELLTKPTAKERSVAEKFKSHGGAQVMEFCSHGTKVECLKAQQATAEMAAKKKQERRDEKELRPDVDAGENVTGKVPKTESAAEDGEIIAEVINNCEAESQESTDGSDTCSSETTDKCTKLHFKKIIQAHTDESLGDCSFLNTCFHMATCKYVHYEVDTLPHINTNKPTDVKTKLSLKRSVDSSCTLYPPQWIQCDLRFLDMTVLGKFAVVMADPPWDIHMELPYGTMSDDEMRALGVPALQDDGLIFLWVTGRAMELGRDCLKLWGYERVDELIWVKTNQLQRIIRTGRTGHWLNHGKEHCLVGMKGNPTNLNRGLDCDVIVAEVRATSHKPDEIYGIIERLSPGTRKIELFGRPHNIQPNWITLGNQLDGIRLVDPELITQFQKRYPDGNCMSPASANAASINGIQK

Gene
mettl3
Protein
N6-adenosine-methyltransferase subunit METTL3
Organism
Danio rerio
Length
584 amino acids
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: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 hematopoietic stem cells specification: m6A methylation and subsequent destabilization of mRNAs, such as notch1a, leads to decreased Notch signaling, promoting endothelial to hematopoietic 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).
Similarity
Belongs to the MT-A70-like family.
Mass
64.627 kDa
Sequence
MSDTWSHIQAHKKQLDSLRERLQRRRKDPTQLGTEVGSVESGSARSDSPGPAIQSPPQVEVEHPPDPELEKRLLGYLSELSLSLPTDSLTITNQLNTSESPVSHSCIQSLLLKFSAQELIEVRQPSITSSSSSTLVTSVDHTKLWAMIGSAGQSQRTAVKRKADDITHQKRALGSSPSIQAPPSPPRKSSVSLATASISQLTASSGGGGGGADKKGRSNKVQASHLDMEIESLLSQQSTKEQQSKKVSQEILELLNTSSAKEQSIVEKFRSRGRAQVQEFCDYGTKEECVQSGDTPQPCTKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDSPPEAEGDALGPQAGAAELGLHSTVGDSNVGKLFPSQWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRKLNIPILQDDGFLFLWVTGRAMELGRECLSLWGYDRVDEIIWVKTNQLQRIIRTGRTGHWLNHGKEHCLVGVKGNPQGFNRGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNVQPNWITLGNQLDGIHLLDPEVVARFKKRYPDGVISKPKNM

Gene
METTL3
Protein
N6-adenosine-methyltransferase catalytic subunit
Organism
Homo sapiens
Length
580 amino acids
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:27627798, PubMed:27373337, PubMed:27281194, PubMed:28297716, PubMed:30428350, PubMed:29506078, PubMed:29348140, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27627798, PubMed:27373337, PubMed:27281194). 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). 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 to cancer cell proliferation by promoting mRNA translation (PubMed:27117702).
Similarity
Belongs to the MT-A70-like family.
Mass
64.474 kDa
Sequence
MSDTWSSIQAHKKQLDSLRERLQRRRKQDSGHLDLRNPEAALSPTFRSDSPVPTAPTSGGPKPSTASAVPELATDPELEKKLLHHLSDLALTLPTDAVSICLAISTPDAPATQDGVESLLQKFAAQELIEVKRGLLQDDAHPTLVTYADHSKLSAMMGAVAEKKGPGEVAGTVTGQKRRAEQDSTTVAAFASSLVSGLNSSASEPAKEPAKKSRKHAASDVDLEIESLLNQQSTKEQQSKKVSQEILELLNTTTAKEQSIVEKFRSRGRAQVQEFCDYGTKEECMKASDADRPCRKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACMDSEAPGSKDHTPSQELALTQSVGGDSSADRLFPPQWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDGFLFLWVTGRAMELGRECLNLWGYERVDEIIWVKTNQLQRIIRTGRTGHWLNHGKEHCLVGVKGNPQGFNQGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNVQPNWITLGNQLDGIHLLDPDVVARFKQRYPDGIISKPKNL

Gene
Mettl3
Protein
N6-adenosine-methyltransferase subunit METTL3
Organism
Mus musculus
Length
580 amino acids
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:25456834, PubMed:24394384, PubMed:25569111, PubMed:28809392, PubMed:28792938, PubMed:28869969, PubMed:28965759). 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, translation efficiency and editing (By similarity). 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 (PubMed:25456834, PubMed:24394384, PubMed:25569111). 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 (PubMed:24209618). M6A also regulates circadian regulation of hepatic lipid metabolism (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (PubMed:28809392, PubMed:28914256). 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 (By similarity). 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 (PubMed:28792938). Inhibits the type I interferon response by mediating m6A methylation of IFNB (By similarity). 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 (PubMed:28965759). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (By similarity). 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 (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (By similarity). 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 (By similarity).
Similarity
Belongs to the MT-A70-like family.
Mass
64.616 kDa
Sequence
MSDTWSSIQAHKKQLDSLRERLQRRRKQDSGHLDLRNPEAALSPTFRSDSPVPTAPTSSGPKPSTTSVAPELATDPELEKKLLHHLSDLALTLPTDAVSIRLAISTPDAPATQDGVESLLQKFAAQELIEVKRGLLQDDAHPTLVTYADHSKLSAMMGAVADKKGLGEVAGTIAGQKRRAEQDLTTVTTFASSLASGLASSASEPAKEPAKKSRKHAASDVDLEIESLLNQQSTKEQQSKKVSQEILELLNTTTAKEQSIVEKFRSRGRAQVQEFCDYGTKEECMKASDADRPCRKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACVDSESPGSKEHMPSQELALTQSVGGDSSADRLFPPQWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDGFLFLWVTGRAMELGRECLNLWGYERVDEIIWVKTNQLQRIIRTGRTGHWLNHGKEHCLVGVKGNPQGFNQGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNVQPNWITLGNQLDGIHLLDPDVVARFKQRYPDGIISKPKNL