ID   MTA70_HUMAN             Reviewed;         580 AA.
AC   Q86U44; O14736; Q86V05; Q9HB32;
DT   25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   25-JUL-2003, sequence version 2.
DT   25-JAN-2012, entry version 79.
DE   RecName: Full=N6-adenosine-methyltransferase 70 kDa subunit;
DE            Short=MT-A70;
DE            EC=2.1.1.62;
DE   AltName: Full=Methyltransferase-like protein 3;
GN   Name=METTL3; Synonyms=MTA70;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), PROTEIN SEQUENCE OF
RP   48-56; 134-149 AND 509-522, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   MEDLINE=98072274; PubMed=9409616;
RA   Bokar J.A., Shambaugh M.E., Polayes D., Matera A.G., Rottman F.M.;
RT   "Purification and cDNA cloning of the AdoMet-binding subunit of the
RT   human mRNA (N6-adenosine)-methyltransferase.";
RL   RNA 3:1233-1247(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Placenta;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=22459283; PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA   Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA   Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA   Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA   Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA   Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA   Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA   Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA   Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA   Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA   Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA   Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA   Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA   Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA   Quetier F., Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Lung, and Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=16964243; DOI=10.1038/nbt1240;
RA   Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT   "A probability-based approach for high-throughput protein
RT   phosphorylation analysis and site localization.";
RL   Nat. Biotechnol. 24:1285-1292(2006).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350 AND THR-356, AND
RP   MASS SPECTROMETRY.
RC   TISSUE=Embryonic kidney;
RX   PubMed=17525332; DOI=10.1126/science.1140321;
RA   Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA   Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA   Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT   "ATM and ATR substrate analysis reveals extensive protein networks
RT   responsive to DNA damage.";
RL   Science 316:1160-1166(2007).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43; SER-219 AND SER-243,
RP   AND MASS SPECTROMETRY.
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Embryonic kidney;
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: N6-methyltransferase that methylates adenosine residues
CC       of some mRNAs. N6-methyladenosine (m6A), which is present at
CC       internal sites of some mRNAs, may play a role in the efficiency of
CC       mRNA splicing, transport or translation.
CC   -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + m(7)G(5')pppAm = S-
CC       adenosyl-L-homocysteine + m(7)G(5')pppm(6)Am.
CC   -!- SUBCELLULAR LOCATION: Nucleus speckle. Note=Colocalizes with
CC       speckles in interphase nuclei. Suggesting that it may be
CC       associated with nuclear pre-mRNA splicing components.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q86U44-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q86U44-2; Sequence=VSP_007864, VSP_007865, VSP_007866;
CC         Note=No experimental confirmation available;
CC   -!- TISSUE SPECIFICITY: Widely expressed at low level. Expressed in
CC       spleen, thymus, prostate, testis, ovary, small intestine, colon
CC       and peripheral blood leukocytes.
CC   -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
CC   -!- SIMILARITY: Belongs to the MT-A70-like family.
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DR   EMBL; AF014837; AAB71850.1; -; Genomic_DNA.
DR   EMBL; AF283991; AAG13956.1; -; Genomic_DNA.
DR   EMBL; AE000658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BX247964; CAD62303.1; -; mRNA.
DR   EMBL; BC003031; AAH03031.1; -; mRNA.
DR   EMBL; BC001650; AAH01650.1; -; mRNA.
DR   EMBL; BC052244; AAH52244.1; -; mRNA.
DR   IPI; IPI00009755; -.
DR   IPI; IPI00328636; -.
DR   RefSeq; NP_062826.2; NM_019852.3.
DR   UniGene; Hs.168799; -.
DR   ProteinModelPortal; Q86U44; -.
DR   STRING; Q86U44; -.
DR   PhosphoSite; Q86U44; -.
DR   DMDM; 33301371; -.
DR   PeptideAtlas; Q86U44; -.
DR   PRIDE; Q86U44; -.
DR   Ensembl; ENST00000298717; ENSP00000298717; ENSG00000165819.
DR   GeneID; 56339; -.
DR   KEGG; hsa:56339; -.
DR   UCSC; uc001wbc.1; human.
DR   CTD; 56339; -.
DR   GeneCards; GC14M021966; -.
DR   H-InvDB; HIX0011511; -.
DR   HGNC; HGNC:17563; METTL3.
DR   HPA; HPA001299; -.
DR   MIM; 612472; gene.
DR   neXtProt; NX_Q86U44; -.
DR   PharmGKB; PA134955499; -.
DR   eggNOG; prNOG14482; -.
DR   GeneTree; ENSGT00550000075058; -.
DR   HOGENOM; HBG738794; -.
DR   HOVERGEN; HBG052521; -.
DR   InParanoid; Q86U44; -.
DR   OMA; YPDGVIS; -.
DR   OrthoDB; EOG4JQ3XC; -.
DR   PhylomeDB; Q86U44; -.
DR   Reactome; REACT_1675; mRNA Processing.
DR   Reactome; REACT_71; Gene Expression.
DR   NextBio; 61981; -.
DR   ArrayExpress; Q86U44; -.
DR   Bgee; Q86U44; -.
DR   CleanEx; HS_METTL3; -.
DR   Genevestigator; Q86U44; -.
DR   GermOnline; ENSG00000165819; Homo sapiens.
DR   GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR   GO; GO:0016422; F:mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity; IMP:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0010467; P:gene expression; TAS:Reactome.
DR   InterPro; IPR007757; MT-A70.
DR   KO; K05925; -.
DR   Pfam; PF05063; MT-A70; 1.
DR   PROSITE; PS51143; MT_A70; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Complete proteome; Direct protein sequencing;
KW   Methyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW   RNA-binding; S-adenosyl-L-methionine; Transferase.
FT   CHAIN         1    580       N6-adenosine-methyltransferase 70 kDa
FT                                subunit.
FT                                /FTId=PRO_0000207630.
FT   MOD_RES      43     43       Phosphoserine.
FT   MOD_RES     219    219       Phosphoserine.
FT   MOD_RES     243    243       Phosphoserine.
FT   MOD_RES     350    350       Phosphoserine.
FT   MOD_RES     356    356       Phosphothreonine.
FT   VAR_SEQ       1    284       Missing (in isoform 2).
FT                                /FTId=VSP_007864.
FT   VAR_SEQ     486    505       GVKGNPQGFNQGLDCDVIVA -> SSSGAQFNRWSTKKNHL
FT                                ISY (in isoform 2).
FT                                /FTId=VSP_007865.
FT   VAR_SEQ     506    580       Missing (in isoform 2).
FT                                /FTId=VSP_007866.
FT   CONFLICT    251    251       N -> I (in Ref. 1; AAB71850).
FT   CONFLICT    263    264       KF -> I (in Ref. 1; AAB71850).
FT   CONFLICT    382    382       D -> V (in Ref. 1; AAB71850).
FT   CONFLICT    568    568       R -> K (in Ref. 4; AAH52244).
SQ   SEQUENCE   580 AA;  64474 MW;  63A7F10195A3C6AC CRC64;
     MSDTWSSIQA HKKQLDSLRE RLQRRRKQDS GHLDLRNPEA ALSPTFRSDS PVPTAPTSGG
     PKPSTASAVP ELATDPELEK KLLHHLSDLA LTLPTDAVSI CLAISTPDAP ATQDGVESLL
     QKFAAQELIE VKRGLLQDDA HPTLVTYADH SKLSAMMGAV AEKKGPGEVA GTVTGQKRRA
     EQDSTTVAAF ASSLVSGLNS SASEPAKEPA KKSRKHAASD VDLEIESLLN QQSTKEQQSK
     KVSQEILELL NTTTAKEQSI VEKFRSRGRA QVQEFCDYGT KEECMKASDA DRPCRKLHFR
     RIINKHTDES LGDCSFLNTC FHMDTCKYVH YEIDACMDSE APGSKDHTPS QELALTQSVG
     GDSSADRLFP PQWICCDIRY LDVSILGKFA VVMADPPWDI HMELPYGTLT DDEMRRLNIP
     VLQDDGFLFL WVTGRAMELG RECLNLWGYE RVDEIIWVKT NQLQRIIRTG RTGHWLNHGK
     EHCLVGVKGN PQGFNQGLDC DVIVAEVRST SHKPDEIYGM IERLSPGTRK IELFGRPHNV
     QPNWITLGNQ LDGIHLLDPD VVARFKQRYP DGIISKPKNL
//