Mettl3
entrez
56335
canonical
uniprot
Q8C3P7
canonical
ensembl
ENSMUSG00000022160
resolver
ensp
ENSMUSP00000022767
resolver
enst
ENSMUST00000022767
resolver
genesymbol
Mettl3
resolver
genesymbol_syn
Mta70
resolver
uniprot
A0A0R4J041
resolver
uniprot
Q9CV54
resolver
uniprot
Q9ERS9
resolver
uniprot
Q9WUI4
resolver
uniprot_entry
A0A0R4J041_MOUSE
resolver
uniprot_entry
MTA70_MOUSE
resolver
uniprot_sec
Q9CV54
resolver
uniprot_sec
Q9ERS9
resolver
uniprot_sec
Q9WUI4
resolver
activity_regulation
ACTIVITY REGULATION: Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (PubMed:25683224). Methyltransferase activity is inhibited by sumoylation (By similarity). {ECO:0000250|UniProtKB:Q86U44, ECO:0000269|PubMed:25683224}.
uniprot
proteins
amino_acid_sequence
MSDTWSSIQAHKKQLDSLRERLQRRRKQDSGHLDLRNPEAALSPTFRSDSPVPTAPTSSGPKPSTTSVAPELATDPELEKKLLHHLSDLALTLPTDAVSIRLAISTPDAPATQDGVESLLQKFAAQELIEVKRGLLQDDAHPTLVTYADHSKLSAMMGAVADKKGLGEVAGTIAGQKRRAEQDLTTVTTFASSLASGLASSASEPAKEPAKKSRKHAASDVDLEIESLLNQQSTKEQQSKKVSQEILELLNTTTAKEQSIVEKFRSRGRAQVQEFCDYGTKEECMKASDADRPCRKLHFRRIINKHTDESLGDCSFLNTCFHMDTCKYVHYEIDACVDSESPGSKEHMPSQELALTQSVGGDSSADRLFPPQWICCDIRYLDVSILGKFAVVMADPPWDIHMELPYGTLTDDEMRRLNIPVLQDDGFLFLWVTGRAMELGRECLNLWGYERVDEIIWVKTNQLQRIIRTGRTGHWLNHGKEHCLVGVKGNPQGFNQGLDCDVIVAEVRSTSHKPDEIYGMIERLSPGTRKIELFGRPHNVQPNWITLGNQLDGIHLLDPDVVARFKQRYPDGIISKPKNL
uniprot
proteins
ec_number
2.1.1.348
uniprot
proteins
function
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:24394384, PubMed:25456834, PubMed:25569111, PubMed:28792938, PubMed:28809392, 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:24394384, PubMed:25456834, 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, PubMed:32943573). Also required for oogenesis (PubMed:32943573). 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). {ECO:0000250|UniProtKB:Q86U44, ECO:0000269|PubMed:24209618, ECO:0000269|PubMed:24394384, ECO:0000269|PubMed:25456834, ECO:0000269|PubMed:25569111, ECO:0000269|PubMed:28637692, ECO:0000269|PubMed:28792938, ECO:0000269|PubMed:28809392, ECO:0000269|PubMed:28869969, ECO:0000269|PubMed:28914256, ECO:0000269|PubMed:28965759, ECO:0000269|PubMed:32943573}.
uniprot
proteins
mass_dalton
64616
uniprot
proteins
mutagenesis
MUTAGEN 395..398; /note="DPPW->APPA: Loss of activity."; /evidence="ECO:0000269|PubMed:24209618, ECO:0000269|PubMed:28792938
uniprot
proteins
post_translational_modification
PTM: Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1. {ECO:0000250|UniProtKB:Q86U44}.
uniprot
proteins
protein_family
MT-A70-like family
uniprot
proteins
pubmed
11389549
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
24209618
uniprot
proteins
pubmed
24394384
uniprot
proteins
pubmed
25456834
uniprot
proteins
pubmed
25569111
uniprot
proteins
pubmed
25683224
uniprot
proteins
pubmed
28637692
uniprot
proteins
pubmed
28792938
uniprot
proteins
pubmed
28809392
uniprot
proteins
pubmed
28869969
uniprot
proteins
pubmed
28914256
uniprot
proteins
pubmed
28965759
uniprot
proteins
pubmed
29535189
uniprot
proteins
pubmed
29547716
uniprot
proteins
pubmed
32943573
uniprot
proteins
pubmed
9409616
uniprot
proteins
sequence_length
580
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28914256}. Nucleus speckle {ECO:0000269|PubMed:24394384, ECO:0000269|PubMed:25683224}. Cytoplasm {ECO:0000250|UniProtKB:Q86U44}. Note=Colocalizes with speckles in interphase nuclei. Suggesting that it may be associated with nuclear pre-mRNA splicing components (PubMed:24394384). 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 site (By similarity). {ECO:0000250|UniProtKB:Q86U44, ECO:0000269|PubMed:24394384}.
uniprot
proteins