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Q8C3P7 (MTA70_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
N6-adenosine-methyltransferase subunit METTL3

EC=2.1.1.62
Alternative name(s):
Methyltransferase-like protein 3
N6-adenosine-methyltransferase 70 kDa subunit
Short name=MT-A70
Gene names
Name:Mettl3
Synonyms:Mta70
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length580 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

N6-methyltransferase that methylates adenosine residues of some mRNAs and acts as a regulator of the circadian clock and self-renewal of embryonic stem cells. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in the efficiency of mRNA splicing and processing and mRNA stability. M6A regulates the length of the circadian clock: acts as a 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 acts as a regulator of mRNA stability: in embryonic stem cells (ESCs), m6A methylation of mRNAs encoding developmental regulators, results in transcript destabilization, maintaining the groung state of ESCs, thereby promoting self-renewal of ESCs. Ref.5 Ref.6

Catalytic activity

S-adenosyl-L-methionine + m7G(5')pppAm = S-adenosyl-L-homocysteine + m7G(5')pppm6Am. Ref.6

Subunit structure

Component of the WMM complex, a N6-methyltransferase complex composed of WTAP, METTL3 and METTL14.

Subcellular location

Nucleus speckle By similarity. Note: Colocalizes with speckles in interphase nuclei. Suggesting that it may be associated with nuclear pre-mRNA splicing components By similarity. Ref.6

Sequence similarities

Belongs to the MT-A70-like family.

Ontologies

Keywords
   Biological processBiological rhythms
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandRNA-binding
S-adenosyl-L-methionine
   Molecular functionMethyltransferase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA methylation

Inferred from sequence or structural similarity. Source: UniProtKB

circadian rhythm

Inferred from mutant phenotype Ref.5. Source: UniProtKB

mRNA destabilization

Inferred from mutant phenotype Ref.6. Source: UniProtKB

mRNA methylation

Inferred from mutant phenotype Ref.5. Source: UniProtKB

mRNA modification

Inferred from sequence orthology Ref.1. Source: MGI

mRNA processing

Inferred from mutant phenotype Ref.5. Source: UniProtKB

stem cell maintenance

Inferred from mutant phenotype Ref.6. Source: UniProtKB

   Cellular_componentMIS complex

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity

Inferred from direct assay Ref.6. Source: UniProtKB

mRNA (N6-adenosine)-methyltransferase activity

Inferred from sequence orthology Ref.1. Source: MGI

protein binding

Inferred from physical interaction Ref.6. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8C3P7-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8C3P7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     34-106: Missing.
     241-299: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 580579N6-adenosine-methyltransferase subunit METTL3
PRO_0000207631

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue431Phosphoserine By similarity
Modified residue2191Phosphoserine By similarity
Modified residue2431Phosphoserine By similarity

Natural variations

Alternative sequence34 – 10673Missing in isoform 2.
VSP_007867
Alternative sequence241 – 29959Missing in isoform 2.
VSP_007868

Experimental info

Mutagenesis395 – 3984DPPW → APPA: Loss of activity. Ref.5
Sequence conflict1621D → E in AAD33673. Ref.2
Sequence conflict1621D → E in BAC39385. Ref.3
Sequence conflict4711R → P in BAB26322. Ref.3
Sequence conflict4751W → L in BAB26322. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 25, 2003. Version 2.
Checksum: 0DBDA2392A37A018

FASTA58064,616
        10         20         30         40         50         60 
MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS PVPTAPTSSG 

        70         80         90        100        110        120 
PKPSTTSVAP ELATDPELEK KLLHHLSDLA LTLPTDAVSI RLAISTPDAP ATQDGVESLL 

       130        140        150        160        170        180 
QKFAAQELIE VKRGLLQDDA HPTLVTYADH SKLSAMMGAV ADKKGLGEVA GTIAGQKRRA 

       190        200        210        220        230        240 
EQDLTTVTTF ASSLASGLAS SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK 

       250        260        270        280        290        300 
KVSQEILELL NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR 

       310        320        330        340        350        360 
RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACVDSE SPGSKEHMPS QELALTQSVG 

       370        380        390        400        410        420 
GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI HMELPYGTLT DDEMRRLNIP 

       430        440        450        460        470        480 
VLQDDGFLFL WVTGRAMELG RECLNLWGYE RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK 

       490        500        510        520        530        540 
EHCLVGVKGN PQGFNQGLDC DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV 

       550        560        570        580 
QPNWITLGNQ LDGIHLLDPD VVARFKQRYP DGIISKPKNL 

« Hide

Isoform 2 [UniParc].

Checksum: 95539DAD61854334
Show »

FASTA44850,157

References

« Hide 'large scale' references
[1]"Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase."
Bokar J.A., Shambaugh M.E., Polayes D., Matera A.G., Rottman F.M.
RNA 3:1233-1247(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
Strain: 129/Sv.
[2]"Expression of genes involved in mammalian meiosis during the transition from egg to embryo."
Hwang S.-Y., Oh B., Knowles B.B., Solter D., Lee J.-S.
Mol. Reprod. Dev. 59:144-158(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: C57BL/6 X DBA/2.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Stomach and Tongue.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Mammary tumor.
[5]"RNA-methylation-dependent RNA processing controls the speed of the circadian clock."
Fustin J.M., Doi M., Yamaguchi Y., Hida H., Nishimura S., Yoshida M., Isagawa T., Morioka M.S., Kakeya H., Manabe I., Okamura H.
Cell 155:793-806(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF 395-ASP--TRP-398.
[6]"N-methyladenosine modification destabilizes developmental regulators in embryonic stem cells."
Wang Y., Li Y., Toth J.I., Petroski M.D., Zhang Z., Zhao J.C.
Nat. Cell Biol. 16:191-198(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH METTL14.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS27053.1. [Q8C3P7-1]
RefSeqNP_062695.2. NM_019721.2.
UniGeneMm.271759.

3D structure databases

ProteinModelPortalQ8C3P7.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid207910. 1 interaction.
DIPDIP-60724N.
IntActQ8C3P7. 1 interaction.
MINTMINT-4102524.

PTM databases

PhosphoSiteQ8C3P7.

Proteomic databases

PaxDbQ8C3P7.
PRIDEQ8C3P7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022767; ENSMUSP00000022767; ENSMUSG00000022160.
GeneID56335.
KEGGmmu:56335.
UCSCuc007tpc.1. mouse. [Q8C3P7-1]

Organism-specific databases

CTD56339.
MGIMGI:1927165. Mettl3.

Phylogenomic databases

eggNOGCOG4725.
GeneTreeENSGT00550000075058.
HOGENOMHOG000012669.
HOVERGENHBG052521.
InParanoidQ8C3P7.
KOK05925.
OrthoDBEOG7PZRWV.
PhylomeDBQ8C3P7.
TreeFamTF323854.

Gene expression databases

ArrayExpressQ8C3P7.
BgeeQ8C3P7.
CleanExMM_METTL3.
GenevestigatorQ8C3P7.

Family and domain databases

Gene3D3.40.50.150. 1 hit.
InterProIPR025848. MT-A70.
IPR007757. MT-A70-like.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PfamPF05063. MT-A70. 1 hit.
[Graphical view]
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS51143. MT_A70. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMETTL3. mouse.
NextBio312322.
PROQ8C3P7.
SOURCESearch...

Entry information

Entry nameMTA70_MOUSE
AccessionPrimary (citable) accession number: Q8C3P7
Secondary accession number(s): Q9CV54, Q9ERS9, Q9WUI4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2003
Last sequence update: July 25, 2003
Last modified: July 9, 2014
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot