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Q86U44

- MTA70_HUMAN

UniProt

Q86U44 - MTA70_HUMAN

Protein

N6-adenosine-methyltransferase 70 kDa subunit

Gene

METTL3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 2 (25 Jul 2003)
      Previous versions | rss
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    Functioni

    N6-methyltransferase that methylates adenosine residues of some mRNAs and acts as a regulator of the circadian clock. 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. M6A regulates the length of the ciracadian 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.3 Publications

    Catalytic activityi

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

    GO - Molecular functioni

    1. mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity Source: UniProtKB
    2. RNA binding Source: UniProtKB-KW

    GO - Biological processi

    1. circadian rhythm Source: UniProtKB
    2. gene expression Source: Reactome
    3. mRNA destabilization Source: UniProtKB
    4. mRNA methylation Source: UniProtKB
    5. mRNA processing Source: UniProtKB
    6. RNA methylation Source: UniProtKB
    7. stem cell maintenance Source: UniProtKB

    Keywords - Molecular functioni

    Methyltransferase, Transferase

    Keywords - Biological processi

    Biological rhythms

    Keywords - Ligandi

    RNA-binding, S-adenosyl-L-methionine

    Enzyme and pathway databases

    ReactomeiREACT_125. Processing of Capped Intron-Containing Pre-mRNA.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    N6-adenosine-methyltransferase 70 kDa subunit (EC:2.1.1.62)
    Short name:
    MT-A70
    Alternative name(s):
    Methyltransferase-like protein 3
    Gene namesi
    Name:METTL3
    Synonyms:MTA70
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:17563. METTL3.

    Subcellular locationi

    Nucleus speckle 1 Publication
    Note: Colocalizes with speckles in interphase nuclei. Suggesting that it may be associated with nuclear pre-mRNA splicing components.

    GO - Cellular componenti

    1. MIS complex Source: UniProtKB
    2. nuclear speck Source: UniProtKB
    3. nucleoplasm Source: Reactome
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134955499.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 580579N6-adenosine-methyltransferase 70 kDa subunitPRO_0000207630Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication
    Modified residuei43 – 431Phosphoserine3 Publications
    Modified residuei219 – 2191Phosphoserine1 Publication
    Modified residuei243 – 2431Phosphoserine1 Publication

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ86U44.
    PaxDbiQ86U44.
    PeptideAtlasiQ86U44.
    PRIDEiQ86U44.

    PTM databases

    PhosphoSiteiQ86U44.

    Expressioni

    Tissue specificityi

    Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.1 Publication

    Gene expression databases

    ArrayExpressiQ86U44.
    BgeeiQ86U44.
    CleanExiHS_METTL3.
    GenevestigatoriQ86U44.

    Organism-specific databases

    HPAiHPA001299.

    Interactioni

    Protein-protein interaction databases

    BioGridi121139. 3 interactions.
    DIPiDIP-60727N.
    STRINGi9606.ENSP00000298717.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86U44.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the MT-A70-like family.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG4725.
    HOGENOMiHOG000012669.
    HOVERGENiHBG052521.
    InParanoidiQ86U44.
    KOiK05925.
    OMAiHTKLWAM.
    OrthoDBiEOG7PZRWV.
    PhylomeDBiQ86U44.
    TreeFamiTF323854.

    Family and domain databases

    Gene3Di3.40.50.150. 1 hit.
    InterProiIPR025848. MT-A70.
    IPR007757. MT-A70-like.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view]
    PfamiPF05063. MT-A70. 1 hit.
    [Graphical view]
    SUPFAMiSSF53335. SSF53335. 1 hit.
    PROSITEiPS51143. MT_A70. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q86U44-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS    50
    PVPTAPTSGG PKPSTASAVP ELATDPELEK KLLHHLSDLA LTLPTDAVSI 100
    CLAISTPDAP ATQDGVESLL QKFAAQELIE VKRGLLQDDA HPTLVTYADH 150
    SKLSAMMGAV AEKKGPGEVA GTVTGQKRRA EQDSTTVAAF ASSLVSGLNS 200
    SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK KVSQEILELL 250
    NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR 300
    RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACMDSE APGSKDHTPS 350
    QELALTQSVG GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI 400
    HMELPYGTLT DDEMRRLNIP VLQDDGFLFL WVTGRAMELG RECLNLWGYE 450
    RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK EHCLVGVKGN PQGFNQGLDC 500
    DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV QPNWITLGNQ 550
    LDGIHLLDPD VVARFKQRYP DGIISKPKNL 580
    Length:580
    Mass (Da):64,474
    Last modified:July 25, 2003 - v2
    Checksum:i63A7F10195A3C6AC
    GO
    Isoform 2 (identifier: Q86U44-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-284: Missing.
         486-505: GVKGNPQGFNQGLDCDVIVA → SSSGAQFNRWSTKKNHLISY
         506-580: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:221
    Mass (Da):25,479
    Checksum:iD95A9087F7B99439
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti251 – 2511N → I in AAB71850. (PubMed:9409616)Curated
    Sequence conflicti263 – 2642KF → I in AAB71850. (PubMed:9409616)Curated
    Sequence conflicti382 – 3821D → V in AAB71850. (PubMed:9409616)Curated
    Sequence conflicti568 – 5681R → K in AAH52244. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 284284Missing in isoform 2. 1 PublicationVSP_007864Add
    BLAST
    Alternative sequencei486 – 50520GVKGN…DVIVA → SSSGAQFNRWSTKKNHLISY in isoform 2. 1 PublicationVSP_007865Add
    BLAST
    Alternative sequencei506 – 58075Missing in isoform 2. 1 PublicationVSP_007866Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF014837 Genomic DNA. Translation: AAB71850.1.
    AF283991 Genomic DNA. Translation: AAG13956.1.
    AE000658 Genomic DNA. No translation available.
    BX247964 mRNA. Translation: CAD62303.1.
    BC003031 mRNA. Translation: AAH03031.1.
    BC001650 mRNA. Translation: AAH01650.1.
    BC052244 mRNA. Translation: AAH52244.1.
    CCDSiCCDS32044.1. [Q86U44-1]
    RefSeqiNP_062826.2. NM_019852.3. [Q86U44-1]
    UniGeneiHs.168799.

    Genome annotation databases

    EnsembliENST00000298717; ENSP00000298717; ENSG00000165819. [Q86U44-1]
    GeneIDi56339.
    KEGGihsa:56339.
    UCSCiuc001wbb.3. human. [Q86U44-1]

    Polymorphism databases

    DMDMi33301371.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF014837 Genomic DNA. Translation: AAB71850.1 .
    AF283991 Genomic DNA. Translation: AAG13956.1 .
    AE000658 Genomic DNA. No translation available.
    BX247964 mRNA. Translation: CAD62303.1 .
    BC003031 mRNA. Translation: AAH03031.1 .
    BC001650 mRNA. Translation: AAH01650.1 .
    BC052244 mRNA. Translation: AAH52244.1 .
    CCDSi CCDS32044.1. [Q86U44-1 ]
    RefSeqi NP_062826.2. NM_019852.3. [Q86U44-1 ]
    UniGenei Hs.168799.

    3D structure databases

    ProteinModelPortali Q86U44.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121139. 3 interactions.
    DIPi DIP-60727N.
    STRINGi 9606.ENSP00000298717.

    PTM databases

    PhosphoSitei Q86U44.

    Polymorphism databases

    DMDMi 33301371.

    Proteomic databases

    MaxQBi Q86U44.
    PaxDbi Q86U44.
    PeptideAtlasi Q86U44.
    PRIDEi Q86U44.

    Protocols and materials databases

    DNASUi 56339.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000298717 ; ENSP00000298717 ; ENSG00000165819 . [Q86U44-1 ]
    GeneIDi 56339.
    KEGGi hsa:56339.
    UCSCi uc001wbb.3. human. [Q86U44-1 ]

    Organism-specific databases

    CTDi 56339.
    GeneCardsi GC14M021966.
    HGNCi HGNC:17563. METTL3.
    HPAi HPA001299.
    MIMi 612472. gene.
    neXtProti NX_Q86U44.
    PharmGKBi PA134955499.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG4725.
    HOGENOMi HOG000012669.
    HOVERGENi HBG052521.
    InParanoidi Q86U44.
    KOi K05925.
    OMAi HTKLWAM.
    OrthoDBi EOG7PZRWV.
    PhylomeDBi Q86U44.
    TreeFami TF323854.

    Enzyme and pathway databases

    Reactomei REACT_125. Processing of Capped Intron-Containing Pre-mRNA.

    Miscellaneous databases

    GeneWikii METTL3.
    GenomeRNAii 56339.
    NextBioi 61981.
    PROi Q86U44.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q86U44.
    Bgeei Q86U44.
    CleanExi HS_METTL3.
    Genevestigatori Q86U44.

    Family and domain databases

    Gene3Di 3.40.50.150. 1 hit.
    InterProi IPR025848. MT-A70.
    IPR007757. MT-A70-like.
    IPR029063. SAM-dependent_MTases-like.
    [Graphical view ]
    Pfami PF05063. MT-A70. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53335. SSF53335. 1 hit.
    PROSITEi PS51143. MT_A70. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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), PROTEIN SEQUENCE OF 48-56; 134-149 AND 509-522, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    2. "Full-length cDNA libraries and normalization."
      Li W.B., Gruber C., Jessee J., Polayes D.
      Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Placenta.
    3. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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: Lung and Pancreas.
    5. "A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
      Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
      Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43; SER-219 AND SER-243, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    8. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    9. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    10. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: FUNCTION.
    13. "N-methyladenosine-dependent regulation of messenger RNA stability."
      Wang X., Lu Z., Gomez A., Hon G.C., Yue Y., Han D., Fu Y., Parisien M., Dai Q., Jia G., Ren B., Pan T., He C.
      Nature 505:117-120(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiMTA70_HUMAN
    AccessioniPrimary (citable) accession number: Q86U44
    Secondary accession number(s): O14736, Q86V05, Q9HB32
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 25, 2003
    Last sequence update: July 25, 2003
    Last modified: October 1, 2014
    This is version 102 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3