UniProtKB - Q8C3P7 (MTA70_MOUSE)
N6-adenosine-methyltransferase subunit METTL3
Mettl3
Functioni
Caution
Catalytic activityi
- adenosine in mRNA + S-adenosyl-L-methionine = H+ + N6-methyladenosine in mRNA + S-adenosyl-L-homocysteine1 PublicationEC:2.1.1.3481 Publication
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 395 | S-adenosyl-L-methionineBy similarity | 1 | |
Binding sitei | 438 | Interaction with METTL14By similarity | 1 | |
Binding sitei | 441 | Interaction with METTL14By similarity | 1 | |
Binding sitei | 513 | S-adenosyl-L-methionineBy similarity | 1 |
GO - Molecular functioni
- methyltransferase activity Source: GO_Central
- mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity Source: InterPro
- mRNA (N6-adenosine)-methyltransferase activity Source: UniProtKB
- mRNA binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- RNA methyltransferase activity Source: MGI
- S-adenosyl-L-methionine binding Source: UniProtKB
GO - Biological processi
- adenosine to inosine editing Source: UniProtKB
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to UV Source: UniProtKB
- circadian rhythm Source: UniProtKB
- dosage compensation by inactivation of X chromosome Source: UniProtKB
- endothelial to hematopoietic transition Source: UniProtKB
- forebrain radial glial cell differentiation Source: UniProtKB
- gliogenesis Source: UniProtKB
- innate immune response Source: UniProtKB-KW
- mRNA catabolic process Source: UniProtKB
- mRNA destabilization Source: UniProtKB
- mRNA methylation Source: UniProtKB
- mRNA modification Source: MGI
- mRNA processing Source: UniProtKB
- mRNA splicing, via spliceosome Source: UniProtKB
- negative regulation of Notch signaling pathway Source: UniProtKB
- negative regulation of type I interferon-mediated signaling pathway Source: UniProtKB
- oogenesis Source: UniProtKB
- positive regulation of cap-independent translational initiation Source: UniProtKB
- positive regulation of translation Source: UniProtKB
- primary miRNA methylation Source: UniProtKB
- primary miRNA processing Source: UniProtKB
- regulation of hematopoietic stem cell differentiation Source: UniProtKB
- regulation of meiotic cell cycle Source: UniProtKB
- regulation of T cell differentiation Source: UniProtKB
- RNA methylation Source: UniProtKB
- spermatogenesis Source: UniProtKB
- stem cell population maintenance Source: UniProtKB
Keywordsi
Molecular function | Methyltransferase, RNA-binding, Transferase |
Biological process | Biological rhythms, Differentiation, DNA damage, Immunity, Innate immunity, Oogenesis, Spermatogenesis |
Ligand | S-adenosyl-L-methionine |
Enzyme and pathway databases
Reactomei | R-MMU-72203, Processing of Capped Intron-Containing Pre-mRNA |
Names & Taxonomyi
Protein namesi | Recommended name: N6-adenosine-methyltransferase subunit METTL3 (EC:2.1.1.3481 Publication)Alternative name(s): Methyltransferase-like protein 3 N6-adenosine-methyltransferase 70 kDa subunit Short name: MT-A70 |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1927165, Mettl3 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus 1 Publication
- Nucleus speckle 2 Publications
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).By similarity1 Publication
Nucleus
- nuclear speck Source: UniProtKB
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB-SubCell
- RNA N6-methyladenosine methyltransferase complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 395 – 398 | DPPW → APPA: Loss of activity. 2 Publications | 4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000207631 | 2 – 580 | N6-adenosine-methyltransferase subunit METTL3Add BLAST | 579 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserine; alternateBy similarity | 1 | |
Modified residuei | 2 | Phosphoserine; alternateBy similarity | 1 | |
Modified residuei | 43 | PhosphoserineBy similarity | 1 | |
Modified residuei | 48 | PhosphoserineBy similarity | 1 | |
Modified residuei | 50 | PhosphoserineBy similarity | 1 | |
Cross-linki | 177 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity | ||
Cross-linki | 211 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity | ||
Cross-linki | 212 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity | ||
Cross-linki | 215 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity | ||
Modified residuei | 219 | PhosphoserineCombined sources | 1 | |
Modified residuei | 243 | PhosphoserineBy similarity | 1 | |
Modified residuei | 350 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q8C3P7 |
jPOSTi | Q8C3P7 |
PaxDbi | Q8C3P7 |
PeptideAtlasi | Q8C3P7 |
PRIDEi | Q8C3P7 |
ProteomicsDBi | 291357 [Q8C3P7-1] 291358 [Q8C3P7-2] |
PTM databases
iPTMneti | Q8C3P7 |
PhosphoSitePlusi | Q8C3P7 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Heterodimer; heterodimerizes with METTL14 to form an antiparallel heterodimer that constitutes an active methyltransferase (By similarity).
Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716).
Interacts with NCBP1/CBP80 (By similarity).
Interacts with EIF4E (By similarity).
Interacts with EIF3B (By similarity).
By similarity2 PublicationsBinary interactionsi
Q8C3P7
With | #Exp. | IntAct |
---|---|---|
Mettl14 [Q3UIK4] | 2 | EBI-8311763,EBI-16089028 |
GO - Molecular functioni
- protein heterodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 207910, 3 interactors |
ComplexPortali | CPX-1609, WMM N6-adenosine-methyltransferase complex |
DIPi | DIP-60724N |
IntActi | Q8C3P7, 2 interactors |
MINTi | Q8C3P7 |
STRINGi | 10090.ENSMUSP00000022767 |
Miscellaneous databases
RNActi | Q8C3P7, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 377 – 378 | S-adenosyl-L-methionine bindingBy similarity | 2 | |
Regioni | 396 – 410 | Gate loop 1By similarityAdd BLAST | 15 | |
Regioni | 450 – 454 | Interaction with METTL14By similarity | 5 | |
Regioni | 462 – 479 | Interphase loopBy similarityAdd BLAST | 18 | |
Regioni | 464 – 480 | Interaction with METTL14By similarityAdd BLAST | 17 | |
Regioni | 465 – 478 | Positively charged region required for RNA-bindingBy similarityAdd BLAST | 14 | |
Regioni | 507 – 515 | Gate loop 2By similarity | 9 | |
Regioni | 536 – 539 | S-adenosyl-L-methionine bindingBy similarity | 4 | |
Regioni | 549 – 550 | S-adenosyl-L-methionine bindingBy similarity | 2 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 210 – 215 | Nuclear localization signalBy similarity | 6 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2098, Eukaryota |
InParanoidi | Q8C3P7 |
OrthoDBi | 788192at2759 |
PhylomeDBi | Q8C3P7 |
TreeFami | TF323854 |
Family and domain databases
InterProi | View protein in InterPro IPR025848, MT-A70 IPR007757, MT-A70-like IPR029063, SAM-dependent_MTases |
Pfami | View protein in Pfam PF05063, MT-A70, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51143, MT_A70, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS
60 70 80 90 100
PVPTAPTSSG PKPSTTSVAP ELATDPELEK KLLHHLSDLA LTLPTDAVSI
110 120 130 140 150
RLAISTPDAP ATQDGVESLL QKFAAQELIE VKRGLLQDDA HPTLVTYADH
160 170 180 190 200
SKLSAMMGAV ADKKGLGEVA GTIAGQKRRA EQDLTTVTTF ASSLASGLAS
210 220 230 240 250
SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK KVSQEILELL
260 270 280 290 300
NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR
310 320 330 340 350
RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACVDSE SPGSKEHMPS
360 370 380 390 400
QELALTQSVG GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI
410 420 430 440 450
HMELPYGTLT DDEMRRLNIP VLQDDGFLFL WVTGRAMELG RECLNLWGYE
460 470 480 490 500
RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK EHCLVGVKGN PQGFNQGLDC
510 520 530 540 550
DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV QPNWITLGNQ
560 570 580
LDGIHLLDPD VVARFKQRYP DGIISKPKNL
Computationally mapped potential isoform sequencesi
There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0R4J041 | A0A0R4J041_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 580 | Annotation score: | ||
G5E922 | G5E922_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 335 | Annotation score: | ||
G3UXX7 | G3UXX7_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 245 | Annotation score: | ||
G3UZP2 | G3UZP2_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 245 | Annotation score: | ||
G3UYB5 | G3UYB5_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 153 | Annotation score: | ||
G3UZP3 | G3UZP3_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 104 | Annotation score: | ||
G3UXN3 | G3UXN3_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 73 | Annotation score: | ||
G3UX68 | G3UX68_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 37 | Annotation score: | ||
G3UY98 | G3UY98_MOUSE | N6-adenosine-methyltransferase subu... | Mettl3 | 36 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 162 | D → E in AAD33673 (PubMed:11389549).Curated | 1 | |
Sequence conflicti | 162 | D → E in BAC39385 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 471 | R → P in BAB26322 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 475 | W → L in BAB26322 (PubMed:16141072).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_007867 | 34 – 106 | Missing in isoform 2. 1 PublicationAdd BLAST | 73 | |
Alternative sequenceiVSP_007868 | 241 – 299 | Missing in isoform 2. 1 PublicationAdd BLAST | 59 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF283992 Genomic DNA Translation: AAG13957.1 AF135789 mRNA Translation: AAD33673.1 AK009492 mRNA Translation: BAB26322.1 AK085189 mRNA Translation: BAC39385.1 BC012526 mRNA Translation: AAH12526.1 |
CCDSi | CCDS27053.1 [Q8C3P7-1] |
RefSeqi | NP_062695.2, NM_019721.2 |
Genome annotation databases
GeneIDi | 56335 |
KEGGi | mmu:56335 |
UCSCi | uc007tpc.1, mouse [Q8C3P7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF283992 Genomic DNA Translation: AAG13957.1 AF135789 mRNA Translation: AAD33673.1 AK009492 mRNA Translation: BAB26322.1 AK085189 mRNA Translation: BAC39385.1 BC012526 mRNA Translation: AAH12526.1 |
CCDSi | CCDS27053.1 [Q8C3P7-1] |
RefSeqi | NP_062695.2, NM_019721.2 |
3D structure databases
SMRi | Q8C3P7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 207910, 3 interactors |
ComplexPortali | CPX-1609, WMM N6-adenosine-methyltransferase complex |
DIPi | DIP-60724N |
IntActi | Q8C3P7, 2 interactors |
MINTi | Q8C3P7 |
STRINGi | 10090.ENSMUSP00000022767 |
PTM databases
iPTMneti | Q8C3P7 |
PhosphoSitePlusi | Q8C3P7 |
Proteomic databases
EPDi | Q8C3P7 |
jPOSTi | Q8C3P7 |
PaxDbi | Q8C3P7 |
PeptideAtlasi | Q8C3P7 |
PRIDEi | Q8C3P7 |
ProteomicsDBi | 291357 [Q8C3P7-1] 291358 [Q8C3P7-2] |
Genome annotation databases
GeneIDi | 56335 |
KEGGi | mmu:56335 |
UCSCi | uc007tpc.1, mouse [Q8C3P7-1] |
Organism-specific databases
CTDi | 56339 |
MGIi | MGI:1927165, Mettl3 |
Phylogenomic databases
eggNOGi | KOG2098, Eukaryota |
InParanoidi | Q8C3P7 |
OrthoDBi | 788192at2759 |
PhylomeDBi | Q8C3P7 |
TreeFami | TF323854 |
Enzyme and pathway databases
Reactomei | R-MMU-72203, Processing of Capped Intron-Containing Pre-mRNA |
Miscellaneous databases
BioGRID-ORCSi | 56335, 23 hits in 52 CRISPR screens |
ChiTaRSi | Mettl3, mouse |
PROi | PR:Q8C3P7 |
RNActi | Q8C3P7, protein |
SOURCEi | Search... |
Family and domain databases
InterProi | View protein in InterPro IPR025848, MT-A70 IPR007757, MT-A70-like IPR029063, SAM-dependent_MTases |
Pfami | View protein in Pfam PF05063, MT-A70, 1 hit |
SUPFAMi | SSF53335, SSF53335, 1 hit |
PROSITEi | View protein in PROSITE PS51143, MT_A70, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MTA70_MOUSE | |
Accessioni | Q8C3P7Primary (citable) accession number: Q8C3P7 Secondary accession number(s): Q9CV54, Q9ERS9, Q9WUI4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 25, 2003 |
Last sequence update: | July 25, 2003 | |
Last modified: | April 7, 2021 | |
This is version 135 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families