MET14_HUMAN
ID MET14_HUMAN Reviewed; 456 AA.
AC Q9HCE5; A6NIG1; Q969V2;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=N6-adenosine-methyltransferase non-catalytic subunit {ECO:0000305};
DE AltName: Full=Methyltransferase-like protein 14 {ECO:0000312|HGNC:HGNC:29330};
DE Short=hMETTL14 {ECO:0000303|PubMed:27373337};
GN Name=METTL14 {ECO:0000312|HGNC:HGNC:29330};
GN Synonyms=KIAA1627 {ECO:0000303|PubMed:10997877};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
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., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=24407421; DOI=10.1038/cr.2014.3;
RA Ping X.L., Sun B.F., Wang L., Xiao W., Yang X., Wang W.J., Adhikari S.,
RA Shi Y., Lv Y., Chen Y.S., Zhao X., Li A., Yang Y., Dahal U., Lou X.M.,
RA Liu X., Huang J., Yuan W.P., Zhu X.F., Cheng T., Zhao Y.L., Wang X.,
RA Danielsen J.M., Liu F., Yang Y.G.;
RT "Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine
RT methyltransferase.";
RL Cell Res. 24:177-189(2014).
RN [9]
RP IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=24981863; DOI=10.1016/j.celrep.2014.05.048;
RA Schwartz S., Mumbach M.R., Jovanovic M., Wang T., Maciag K., Bushkin G.G.,
RA Mertins P., Ter-Ovanesyan D., Habib N., Cacchiarelli D., Sanjana N.E.,
RA Freinkman E., Pacold M.E., Satija R., Mikkelsen T.S., Hacohen N., Zhang F.,
RA Carr S.A., Lander E.S., Regev A.;
RT "Perturbation of m6A writers reveals two distinct classes of mRNA
RT methylation at internal and 5' sites.";
RL Cell Rep. 8:284-296(2014).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-399, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=24316715; DOI=10.1038/nchembio.1432;
RA Liu J., Yue Y., Han D., Wang X., Fu Y., Zhang L., Jia G., Yu M., Lu Z.,
RA Deng X., Dai Q., Chen W., He C.;
RT "A METTL3-METTL14 complex mediates mammalian nuclear RNA N-adenosine
RT methylation.";
RL Nat. Chem. Biol. 10:93-95(2014).
RN [12]
RP FUNCTION.
RX PubMed=25719671; DOI=10.1038/nature14234;
RA Liu N., Dai Q., Zheng G., He C., Parisien M., Pan T.;
RT "N(6)-methyladenosine-dependent RNA structural switches regulate RNA-
RT protein interactions.";
RL Nature 518:560-564(2015).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=26458103; DOI=10.1038/nature15377;
RA Zhou J., Wan J., Gao X., Zhang X., Jaffrey S.R., Qian S.B.;
RT "Dynamic m(6)A mRNA methylation directs translational control of heat shock
RT response.";
RL Nature 526:591-594(2015).
RN [14]
RP IDENTIFICATION IN THE WMM COMPLEX.
RX PubMed=29507755; DOI=10.1038/s41421-018-0019-0;
RA Yue Y., Liu J., Cui X., Cao J., Luo G., Zhang Z., Cheng T., Gao M., Shu X.,
RA Ma H., Wang F., Wang X., Shen B., Wang Y., Feng X., He C., Liu J.;
RT "VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop
RT codon and associates with alternative polyadenylation.";
RL Cell Discov. 4:10-10(2018).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, RNA-BINDING, IDENTIFICATION IN THE WMM
RP COMPLEX, PHOSPHORYLATION AT SER-399, AND MUTAGENESIS OF 63-LYS--LYS-65 AND
RP SER-399.
RX PubMed=29348140; DOI=10.1261/rna.064063.117;
RA Schoeller E., Weichmann F., Treiber T., Ringle S., Treiber N., Flatley A.,
RA Feederle R., Bruckmann A., Meister G.;
RT "Interactions, localization, and phosphorylation of the m6A generating
RT METTL3-METTL14-WTAP complex.";
RL RNA 24:499-512(2018).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 107-395 IN COMPLEX WITH METTL3,
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLU-192; TYR-198; 254-ARG-ARG-255;
RP CYS-338 AND 362-PRO-THR-363.
RX PubMed=27627798; DOI=10.7554/elife.18434;
RA Sledz P., Jinek M.;
RT "Structural insights into the molecular mechanism of the m(6)A writer
RT complex.";
RL Elife 5:E18434-E18434(2016).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 111-456 IN COMPLEX WITH METTL3,
RP FUNCTION, SUBUNIT, RNA-BINDING, AND MUTAGENESIS OF GLU-192; ARG-298 AND
RP ASP-312.
RX PubMed=27373337; DOI=10.1016/j.molcel.2016.05.041;
RA Wang P., Doxtader K.A., Nam Y.;
RT "Structural basis for cooperative function of Mettl3 and Mettl14
RT methyltransferases.";
RL Mol. Cell 63:306-317(2016).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.61 ANGSTROMS) OF 109-408 IN COMPLEX WITH METTL3,
RP FUNCTION, SUBUNIT, RNA-BINDING, PHOSPHORYLATION AT SER-399, AND MUTAGENESIS
RP OF ASP-173; GLU-192; ARG-245; ARG-255 AND 297-LYS-ARG-298.
RX PubMed=27281194; DOI=10.1038/nature18298;
RA Wang X., Feng J., Xue Y., Guan Z., Zhang D., Liu Z., Gong Z., Wang Q.,
RA Huang J., Tang C., Zou T., Yin P.;
RT "Structural basis of N(6)-adenosine methylation by the METTL3-METTL14
RT complex.";
RL Nature 534:575-578(2016).
CC -!- FUNCTION: The METTL3-METTL14 heterodimer forms a N6-methyltransferase
CC complex that methylates adenosine residues at the N(6) position of some
CC mRNAs and regulates the circadian clock, differentiation of embryonic
CC stem cells and cortical neurogenesis (PubMed:24316715, PubMed:24407421,
CC PubMed:25719671, PubMed:29348140, PubMed:27373337, PubMed:27281194). In
CC the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding
CC scaffold that recognizes the substrate rather than the catalytic core
CC (PubMed:27627798, PubMed:27373337, PubMed:27281194, PubMed:29348140).
CC N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3'
CC consensus sites of some mRNAs, plays a role in mRNA stability and
CC processing (PubMed:24316715, PubMed:24407421, PubMed:25719671). M6A
CC acts as a key regulator of mRNA stability by promoting mRNA
CC destabilization and degradation (By similarity). In embryonic stem
CC cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-
CC promoting transcripts results in transcript destabilization (By
CC similarity). M6A regulates spermatogonial differentiation and meiosis
CC and is essential for male fertility and spermatogenesis (By
CC similarity). M6A also regulates cortical neurogenesis: m6A methylation
CC of transcripts related to transcription factors, neural stem cells, the
CC cell cycle and neuronal differentiation during brain development
CC promotes their destabilization and decay, promoting differentiation of
CC radial glial cells (By similarity). {ECO:0000250|UniProtKB:Q3UIK4,
CC ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:24407421,
CC ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:27281194,
CC ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27627798,
CC ECO:0000269|PubMed:29348140}.
CC -!- SUBUNIT: Heterodimer; heterodimerizes with METTL3 to form an
CC antiparallel heterodimer that constitutes an active methyltransferase
CC (PubMed:27627798, PubMed:27373337, PubMed:27281194). Component of the
CC WMM complex, a N6-methyltransferase complex composed of a catalytic
CC subcomplex, named MAC, and of an associated subcomplex, named MACOM
CC (PubMed:24407421, PubMed:24981863, PubMed:24316715, PubMed:29507755,
CC PubMed:29348140). The MAC subcomplex is composed of METTL3 and METTL14
CC (PubMed:24407421, PubMed:24981863, PubMed:24316715, PubMed:29507755).
CC The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA,
CC and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29507755).
CC {ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:24407421,
CC ECO:0000269|PubMed:24981863, ECO:0000269|PubMed:27281194,
CC ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27627798,
CC ECO:0000269|PubMed:29348140, ECO:0000269|PubMed:29507755}.
CC -!- INTERACTION:
CC Q9HCE5; Q86U44: METTL3; NbExp=20; IntAct=EBI-6661081, EBI-11105430;
CC Q9HCE5; Q86U44-1: METTL3; NbExp=10; IntAct=EBI-6661081, EBI-16084936;
CC Q9HCE5; Q15007-1: WTAP; NbExp=5; IntAct=EBI-6661081, EBI-16084961;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24316715,
CC ECO:0000269|PubMed:24407421, ECO:0000269|PubMed:26458103,
CC ECO:0000269|PubMed:29348140}.
CC -!- SIMILARITY: Belongs to the MT-A70-like family. {ECO:0000255|PROSITE-
CC ProRule:PRU00489}.
CC -!- CAUTION: The effect of phosphorylation at Ser-399 is unclear. According
CC to a report, phosphorylation at Ser-399 is important for interaction
CC with METTL3: phosphorylated Ser-399 forms a salt bridge with 'Arg-471'
CC of METTL3 (PubMed:27281194). According to another report,
CC phosphorylation at Ser-399 does not affect interaction with METTL3
CC (PubMed:29348140). {ECO:0000269|PubMed:27281194,
CC ECO:0000269|PubMed:29348140}.
CC -!- CAUTION: The ability of METTL14 to have catalytic activity is unclear
CC and a number of experimental evidence suggests that it has no
CC methyltransferase activity by itself (PubMed:27627798, PubMed:27281194,
CC PubMed:27373337). According to some reports, has some methyltransferase
CC activity in vitro (PubMed:24316715). However, other studies showed that
CC METTL14 constitutes the RNA-binding scaffold that recognizes the
CC substrate rather than the catalytic core (PubMed:27627798,
CC PubMed:27281194, PubMed:27373337). 3D-structure studies showed that
CC METTL14 contains a degenerate active site that is unable to accommodate
CC donor and acceptor substrates (PubMed:27627798).
CC {ECO:0000269|PubMed:24316715, ECO:0000269|PubMed:27281194,
CC ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27627798}.
CC -!- CAUTION: A disulfide bond between Cys-338 and Cys-388 is observed in a
CC structure (PubMed:27627798). Its existence is however unsure in vivo.
CC {ECO:0000269|PubMed:27627798}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13453.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB046847; BAB13453.1; ALT_INIT; mRNA.
DR EMBL; AK055555; BAB70954.1; -; mRNA.
DR EMBL; AC110079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471229; EAW73651.1; -; Genomic_DNA.
DR EMBL; BC006565; AAH06565.1; -; mRNA.
DR EMBL; BC007449; AAH07449.1; -; mRNA.
DR CCDS; CCDS34053.1; -.
DR RefSeq; NP_066012.1; NM_020961.3.
DR PDB; 5IL0; X-ray; 1.88 A; B=109-408.
DR PDB; 5IL1; X-ray; 1.71 A; B=109-408.
DR PDB; 5IL2; X-ray; 1.61 A; B=109-408.
DR PDB; 5K7M; X-ray; 1.65 A; B=111-456.
DR PDB; 5K7U; X-ray; 1.70 A; B=111-456.
DR PDB; 5K7W; X-ray; 1.65 A; B=111-456.
DR PDB; 5L6D; X-ray; 1.85 A; B=107-395.
DR PDB; 5L6E; X-ray; 1.90 A; B=107-395.
DR PDB; 5TEY; X-ray; 1.80 A; B=1-399.
DR PDB; 6TTP; X-ray; 2.00 A; B=1-456.
DR PDB; 6TTT; X-ray; 2.30 A; B=1-456.
DR PDB; 6TTV; X-ray; 2.14 A; B=1-456.
DR PDB; 6TTW; X-ray; 2.20 A; B=1-456.
DR PDB; 6TTX; X-ray; 2.00 A; B=1-456.
DR PDB; 6TU1; X-ray; 2.31 A; B=1-456.
DR PDB; 6Y4G; X-ray; 1.90 A; B=1-456.
DR PDB; 7ACD; X-ray; 2.50 A; B=106-395.
DR PDB; 7NHG; X-ray; 2.50 A; B=106-395.
DR PDB; 7NHH; X-ray; 2.10 A; B=106-395.
DR PDB; 7NHI; X-ray; 1.85 A; B=106-395.
DR PDB; 7NHJ; X-ray; 2.16 A; B=106-395.
DR PDB; 7NHV; X-ray; 1.91 A; B=106-395.
DR PDB; 7NI7; X-ray; 2.50 A; B=106-395.
DR PDB; 7NI8; X-ray; 2.20 A; B=106-395.
DR PDB; 7NI9; X-ray; 2.20 A; B=106-395.
DR PDB; 7NIA; X-ray; 2.30 A; B=106-395.
DR PDB; 7NID; X-ray; 2.30 A; B=106-395.
DR PDB; 7O08; X-ray; 2.00 A; B=106-395.
DR PDB; 7O09; X-ray; 1.80 A; B=106-395.
DR PDB; 7O0L; X-ray; 1.90 A; B=106-395.
DR PDB; 7O0M; X-ray; 2.39 A; B=106-395.
DR PDB; 7O0P; X-ray; 2.70 A; B=106-395.
DR PDB; 7O0Q; X-ray; 2.49 A; B=106-395.
DR PDB; 7O0R; X-ray; 2.30 A; B=106-395.
DR PDB; 7O27; X-ray; 2.40 A; B=106-395.
DR PDB; 7O28; X-ray; 2.47 A; B=106-395.
DR PDB; 7O29; X-ray; 2.75 A; B=106-395.
DR PDB; 7O2E; X-ray; 2.50 A; B=106-395.
DR PDB; 7O2F; X-ray; 2.10 A; B=106-395.
DR PDB; 7O2H; X-ray; 2.50 A; B=106-395.
DR PDB; 7O2I; X-ray; 3.00 A; B=107-395.
DR PDB; 7O2X; X-ray; 2.80 A; B=106-395.
DR PDB; 7OED; X-ray; 2.00 A; B=106-395.
DR PDB; 7OEE; X-ray; 2.70 A; B=106-395.
DR PDB; 7OEF; X-ray; 2.03 A; B=106-395.
DR PDB; 7OEG; X-ray; 2.79 A; B=106-395.
DR PDB; 7OEH; X-ray; 2.01 A; B=106-395.
DR PDB; 7OEI; X-ray; 2.48 A; B=106-395.
DR PDB; 7OEJ; X-ray; 2.30 A; B=106-395.
DR PDB; 7OEK; X-ray; 1.90 A; B=106-395.
DR PDB; 7OEL; X-ray; 1.86 A; B=106-395.
DR PDB; 7OEM; X-ray; 2.20 A; B=106-395.
DR PDB; 7OQL; X-ray; 2.50 A; B=106-395.
DR PDB; 7OQO; X-ray; 3.35 A; B=106-395.
DR PDB; 7OQP; X-ray; 2.00 A; B=106-395.
DR PDBsum; 5IL0; -.
DR PDBsum; 5IL1; -.
DR PDBsum; 5IL2; -.
DR PDBsum; 5K7M; -.
DR PDBsum; 5K7U; -.
DR PDBsum; 5K7W; -.
DR PDBsum; 5L6D; -.
DR PDBsum; 5L6E; -.
DR PDBsum; 5TEY; -.
DR PDBsum; 6TTP; -.
DR PDBsum; 6TTT; -.
DR PDBsum; 6TTV; -.
DR PDBsum; 6TTW; -.
DR PDBsum; 6TTX; -.
DR PDBsum; 6TU1; -.
DR PDBsum; 6Y4G; -.
DR PDBsum; 7ACD; -.
DR PDBsum; 7NHG; -.
DR PDBsum; 7NHH; -.
DR PDBsum; 7NHI; -.
DR PDBsum; 7NHJ; -.
DR PDBsum; 7NHV; -.
DR PDBsum; 7NI7; -.
DR PDBsum; 7NI8; -.
DR PDBsum; 7NI9; -.
DR PDBsum; 7NIA; -.
DR PDBsum; 7NID; -.
DR PDBsum; 7O08; -.
DR PDBsum; 7O09; -.
DR PDBsum; 7O0L; -.
DR PDBsum; 7O0M; -.
DR PDBsum; 7O0P; -.
DR PDBsum; 7O0Q; -.
DR PDBsum; 7O0R; -.
DR PDBsum; 7O27; -.
DR PDBsum; 7O28; -.
DR PDBsum; 7O29; -.
DR PDBsum; 7O2E; -.
DR PDBsum; 7O2F; -.
DR PDBsum; 7O2H; -.
DR PDBsum; 7O2I; -.
DR PDBsum; 7O2X; -.
DR PDBsum; 7OED; -.
DR PDBsum; 7OEE; -.
DR PDBsum; 7OEF; -.
DR PDBsum; 7OEG; -.
DR PDBsum; 7OEH; -.
DR PDBsum; 7OEI; -.
DR PDBsum; 7OEJ; -.
DR PDBsum; 7OEK; -.
DR PDBsum; 7OEL; -.
DR PDBsum; 7OEM; -.
DR PDBsum; 7OQL; -.
DR PDBsum; 7OQO; -.
DR PDBsum; 7OQP; -.
DR AlphaFoldDB; Q9HCE5; -.
DR SMR; Q9HCE5; -.
DR BioGRID; 121744; 347.
DR ComplexPortal; CPX-1605; WMM N6-adenosine-methyltransferase complex.
DR DIP; DIP-60726N; -.
DR IntAct; Q9HCE5; 337.
DR STRING; 9606.ENSP00000373474; -.
DR ChEMBL; CHEMBL4106140; -.
DR iPTMnet; Q9HCE5; -.
DR PhosphoSitePlus; Q9HCE5; -.
DR BioMuta; METTL14; -.
DR DMDM; 172045930; -.
DR EPD; Q9HCE5; -.
DR jPOST; Q9HCE5; -.
DR MassIVE; Q9HCE5; -.
DR MaxQB; Q9HCE5; -.
DR PaxDb; Q9HCE5; -.
DR PeptideAtlas; Q9HCE5; -.
DR PRIDE; Q9HCE5; -.
DR ProteomicsDB; 81687; -.
DR Antibodypedia; 26610; 135 antibodies from 22 providers.
DR DNASU; 57721; -.
DR Ensembl; ENST00000388822.10; ENSP00000373474.3; ENSG00000145388.15.
DR GeneID; 57721; -.
DR KEGG; hsa:57721; -.
DR MANE-Select; ENST00000388822.10; ENSP00000373474.3; NM_020961.4; NP_066012.1.
DR UCSC; uc003icf.4; human.
DR CTD; 57721; -.
DR DisGeNET; 57721; -.
DR GeneCards; METTL14; -.
DR HGNC; HGNC:29330; METTL14.
DR HPA; ENSG00000145388; Low tissue specificity.
DR MIM; 616504; gene.
DR neXtProt; NX_Q9HCE5; -.
DR OpenTargets; ENSG00000145388; -.
DR PharmGKB; PA164722277; -.
DR VEuPathDB; HostDB:ENSG00000145388; -.
DR eggNOG; KOG2097; Eukaryota.
DR GeneTree; ENSGT00550000075003; -.
DR HOGENOM; CLU_046318_1_0_1; -.
DR InParanoid; Q9HCE5; -.
DR OMA; NINKPGH; -.
DR OrthoDB; 788192at2759; -.
DR PhylomeDB; Q9HCE5; -.
DR TreeFam; TF323641; -.
DR BRENDA; 2.1.1.348; 2681.
DR PathwayCommons; Q9HCE5; -.
DR Reactome; R-HSA-72203; Processing of Capped Intron-Containing Pre-mRNA.
DR SignaLink; Q9HCE5; -.
DR BioGRID-ORCS; 57721; 631 hits in 1099 CRISPR screens.
DR ChiTaRS; METTL14; human.
DR GenomeRNAi; 57721; -.
DR Pharos; Q9HCE5; Tbio.
DR PRO; PR:Q9HCE5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9HCE5; protein.
DR Bgee; ENSG00000145388; Expressed in calcaneal tendon and 194 other tissues.
DR ExpressionAtlas; Q9HCE5; baseline and differential.
DR Genevisible; Q9HCE5; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0036396; C:RNA N6-methyladenosine methyltransferase complex; IDA:UniProtKB.
DR GO; GO:0016422; F:mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0021861; P:forebrain radial glial cell differentiation; ISS:UniProtKB.
DR GO; GO:0042063; P:gliogenesis; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IEA:Ensembl.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0080009; P:mRNA methylation; IDA:UniProtKB.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:1901533; P:negative regulation of hematopoietic progenitor cell differentiation; IMP:ARUK-UCL.
DR GO; GO:0045727; P:positive regulation of translation; IMP:ARUK-UCL.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB.
DR InterPro; IPR045123; METTL14-like.
DR InterPro; IPR007757; MT-A70-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR13107; PTHR13107; 1.
DR Pfam; PF05063; MT-A70; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51143; MT_A70; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Differentiation; Nucleus; Phosphoprotein; Reference proteome;
KW RNA-binding; Spermatogenesis.
FT CHAIN 1..456
FT /note="N6-adenosine-methyltransferase non-catalytic
FT subunit"
FT /id="PRO_0000325790"
FT REGION 50..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..136
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT REGION 237..238
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT REGION 245..254
FT /note="Positively charged region required for RNA-binding"
FT /evidence="ECO:0000269|PubMed:27281194"
FT REGION 255..258
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT REGION 278..287
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT REGION 297..298
FT /note="Positively charged region required for RNA-binding"
FT /evidence="ECO:0000269|PubMed:27281194"
FT REGION 308..312
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT REGION 393..456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 146
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT SITE 242
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT SITE 245
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT SITE 298
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT SITE 399
FT /note="Interaction with METTL3"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0007744|PDB:5IL0, ECO:0007744|PDB:5IL1,
FT ECO:0007744|PDB:5IL2"
FT MOD_RES 399
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0000269|PubMed:29348140, ECO:0007744|PDB:5IL0,
FT ECO:0007744|PDB:5IL1, ECO:0007744|PDB:5IL2,
FT ECO:0007744|PubMed:24275569"
FT MUTAGEN 63..65
FT /note="KRK->GGG: Does not affect nuclear localization."
FT /evidence="ECO:0000269|PubMed:29348140"
FT MUTAGEN 173
FT /note="D->A: Little or no effect on S-adenosyl-L-
FT methionine-binding or methyltransferase activity; when
FT associated with A-192."
FT /evidence="ECO:0000269|PubMed:27281194"
FT MUTAGEN 192
FT /note="E->A: Little or no effect on methyltransferase
FT activity. Little or no effect on S-adenosyl-L-methionine-
FT binding or methyltransferase activity; when associated with
FT A-173."
FT /evidence="ECO:0000269|PubMed:27281194,
FT ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27627798"
FT MUTAGEN 198
FT /note="Y->A: Does not affect methyltransferase activity of
FT the heterodimer complex formed with METTL3."
FT /evidence="ECO:0000269|PubMed:27627798"
FT MUTAGEN 245
FT /note="R->E: Reduced RNA-binding. Reduced RNA-binding; when
FT associated with E-255."
FT /evidence="ECO:0000269|PubMed:27281194"
FT MUTAGEN 254..255
FT /note="RR->AA: Strongly reduced methyltransferase activity
FT of the heterodimer complex formed with METTL3."
FT /evidence="ECO:0000269|PubMed:27627798"
FT MUTAGEN 255
FT /note="R->E: Reduced RNA-binding; when associated with E-
FT 245."
FT /evidence="ECO:0000269|PubMed:27281194"
FT MUTAGEN 297..298
FT /note="KR->EE: Reduced RNA-binding."
FT /evidence="ECO:0000269|PubMed:27281194"
FT MUTAGEN 298
FT /note="R->P: Strongly decreased methyltransferase activity
FT of the heterodimer complex formed with METTL3, probably due
FT to reduced RNA-binding."
FT /evidence="ECO:0000269|PubMed:27373337"
FT MUTAGEN 312
FT /note="D->A: Decreased methyltransferase activity of the
FT heterodimer complex formed with METTL3."
FT /evidence="ECO:0000269|PubMed:27373337"
FT MUTAGEN 338
FT /note="C->A: Does not affect methyltransferase activity of
FT the heterodimer complex formed with METTL3."
FT /evidence="ECO:0000269|PubMed:27627798"
FT MUTAGEN 362..363
FT /note="PT->AA: Little or no effect on methyltransferase
FT activity of the heterodimer complex formed with METTL3."
FT /evidence="ECO:0000269|PubMed:27627798"
FT MUTAGEN 399
FT /note="S->A,E: Does not affect interaction with METTL3."
FT /evidence="ECO:0000269|PubMed:29348140"
FT HELIX 119..126
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 130..133
FT /evidence="ECO:0007829|PDB:5IL2"
FT TURN 140..145
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 147..163
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:5IL2"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 196..200
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 213..217
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 225..234
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 240..251
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 254..264
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:5K7M"
FT STRAND 285..294
FT /evidence="ECO:0007829|PDB:5IL2"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:5IL2"
FT TURN 302..304
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 309..317
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 329..337
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 343..346
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 358..361
FT /evidence="ECO:0007829|PDB:5IL2"
FT HELIX 371..376
FT /evidence="ECO:0007829|PDB:5IL2"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:6TTP"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:5TEY"
FT HELIX 390..395
FT /evidence="ECO:0007829|PDB:5IL2"
SQ SEQUENCE 456 AA; 52150 MW; 73A45B66BB76E241 CRC64;
MDSRLQEIRE RQKLRRQLLA QQLGAESADS IGAVLNSKDE QREIAETRET CRASYDTSAP
NAKRKYLDEG ETDEDKMEEY KDELEMQQDE ENLPYEEEIY KDSSTFLKGT QSLNPHNDYC
QHFVDTGHRP QNFIRDVGLA DRFEEYPKLR ELIRLKDELI AKSNTPPMYL QADIEAFDIR
ELTPKFDVIL LEPPLEEYYR ETGITANEKC WTWDDIMKLE IDEIAAPRSF IFLWCGSGEG
LDLGRVCLRK WGYRRCEDIC WIKTNKNNPG KTKTLDPKAV FQRTKEHCLM GIKGTVKRST
DGDFIHANVD IDLIITEEPE IGNIEKPVEI FHIIEHFCLG RRRLHLFGRD STIRPGWLTV
GPTLTNSNYN AETYASYFSA PNSYLTGCTE EIERLRPKSP PPKSKSDRGG GAPRGGGRGG
TSAGRGRERN RSNFRGERGG FRGGRGGAHR GGFPPR
