EFNMT_HUMAN
ID EFNMT_HUMAN Reviewed; 699 AA.
AC Q8N6R0; A6NFK0; A8K6S5; O94940; Q53EZ6; Q5TGP9; Q5TGQ0; Q8N2P8; Q96J11;
AC Q96SQ0; Q9Y2Z1; Q9Y3M6;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=eEF1A lysine and N-terminal methyltransferase {ECO:0000303|PubMed:30143613, ECO:0000305};
DE Short=eEF1A-KNMT {ECO:0000303|PubMed:30143613};
DE AltName: Full=Methyltransferase-like protein 13 {ECO:0000303|PubMed:26763933, ECO:0000312|HGNC:HGNC:24248};
DE Includes:
DE RecName: Full=eEF1A lysine methyltransferase {ECO:0000303|PubMed:30143613, ECO:0000303|PubMed:30612740};
DE EC=2.1.1.- {ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740};
DE Includes:
DE RecName: Full=eEF1A N-terminal methyltransferase {ECO:0000303|PubMed:30143613};
DE EC=2.1.1.- {ECO:0000269|PubMed:30143613};
GN Name=METTL13 {ECO:0000312|HGNC:HGNC:24248};
GN Synonyms=EEF1AKNMT {ECO:0000303|PubMed:30143613},
GN FEAT {ECO:0000303|PubMed:27659353}, KIAA0859 {ECO:0000312|HGNC:HGNC:24248};
GN ORFNames=CGI-01;
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] (ISOFORM 4).
RA Rhodes S.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 5), AND VARIANT
RP VAL-105.
RC TISSUE=Embryo, Placenta, and Teratocarcinoma;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, and Testis;
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-267, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [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., 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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-267, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP IDENTIFICATION BY 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 [14]
RP SUBCELLULAR LOCATION.
RX PubMed=27659353; DOI=10.1186/s12967-016-1034-2;
RA Li Y., Kobayashi K., Mona M.M., Satomi C., Okano S., Inoue H., Tani K.,
RA Takahashi A.;
RT "Immunogenic FEAT protein circulates in the bloodstream of cancer
RT patients.";
RL J. Transl. Med. 14:275-275(2016).
RN [15]
RP FUNCTION.
RX PubMed=26763933; DOI=10.1038/srep19261;
RA Zhang Z., Zhang G., Kong C., Zhan B., Dong X., Man X.;
RT "METTL13 is downregulated in bladder carcinoma and suppresses cell
RT proliferation, migration and invasion.";
RL Sci. Rep. 6:19261-19261(2016).
RN [16]
RP INTERACTION WITH GAB1 AND SPRY2, POLYMORPHISM, AND VARIANT GLN-544.
RX PubMed=29408807; DOI=10.1172/jci97350;
RA Yousaf R., Ahmed Z.M., Giese A.P., Morell R.J., Lagziel A., Dabdoub A.,
RA Wilcox E.R., Riazuddin S., Friedman T.B., Riazuddin S.;
RT "Modifier variant of METTL13 suppresses human GAB1-associated profound
RT deafness.";
RL J. Clin. Invest. 128:1509-1522(2018).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, INVOLVEMENT IN TUMORIGENESIS, AND MUTAGENESIS
RP OF VAL-54; GLY-58; ASN-59; TYR-67; TYR-71; ASN-76; PHE-115; 120-ASP-LYS-121
RP AND TYR-156.
RX PubMed=30612740; DOI=10.1016/j.cell.2018.11.038;
RA Liu S., Hausmann S., Carlson S.M., Fuentes M.E., Francis J.W., Pillai R.,
RA Lofgren S.M., Hulea L., Tandoc K., Lu J., Li A., Nguyen N.D., Caporicci M.,
RA Kim M.P., Maitra A., Wang H., Wistuba I.I., Porco J.A. Jr., Bassik M.C.,
RA Elias J.E., Song J., Topisirovic I., Van Rechem C., Mazur P.K., Gozani O.;
RT "METTL13 methylation of eEF1A increases translational output to promote
RT tumorigenesis.";
RL Cell 0:0-0(2018).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 470-699, FUNCTION, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-524; ASP-551;
RP ASP-575; VAL-576; ASP-577; SER-578 AND ASN-647.
RX PubMed=30143613; DOI=10.1038/s41467-018-05646-y;
RA Jakobsson M.E., Malecki J.M., Halabelian L., Nilges B.S., Pinto R.,
RA Kudithipudi S., Munk S., Davydova E., Zuhairi F.R., Arrowsmith C.H.,
RA Jeltsch A., Leidel S.A., Olsen J.V., Falnes P.O.;
RT "The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A
RT and modulates codon-specific translation rates.";
RL Nat. Commun. 9:3411-3411(2018).
RN [19]
RP VARIANT CYS-16.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Dual methyltransferase that catalyzes methylation of
CC elongation factor 1-alpha (EEF1A1 and EEF1A2) at two different
CC positions, and is therefore involved in the regulation of mRNA
CC translation (PubMed:30612740, PubMed:30143613). Via its C-terminus,
CC methylates EEF1A1 and EEF1A2 at the N-terminal residue 'Gly-2'
CC (PubMed:30143613). Via its N-terminus dimethylates EEF1A1 and EEF1A2 at
CC residue 'Lys-55' (PubMed:30612740, PubMed:30143613). Has no activity
CC towards core histones H2A, H2B, H3 and H4 (PubMed:30612740). Negatively
CC regulates cell proliferation at G1/S transition via transcriptional
CC suppression of cell cycle regulatory genes such as CDK4 and CDK6
CC (PubMed:26763933). {ECO:0000269|PubMed:26763933,
CC ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)-
CC methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929;
CC Evidence={ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51737;
CC Evidence={ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+)
CC + N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:54196, Rhea:RHEA-COMP:13053, Rhea:RHEA-COMP:13827,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54197;
CC Evidence={ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-terminal glycyl-L-lysyl-L-glutamyl-[protein] + 3 S-adenosyl-
CC L-methionine = 3 H(+) + N-terminal N,N,N-trimethyl-glycyl-L-lysyl-L-
CC glutamyl-[protein] + 3 S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:58440, Rhea:RHEA-COMP:15140, Rhea:RHEA-COMP:15143,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:142597, ChEBI:CHEBI:142600;
CC Evidence={ECO:0000269|PubMed:30143613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58441;
CC Evidence={ECO:0000269|PubMed:30143613, ECO:0000269|PubMed:30612740};
CC -!- ACTIVITY REGULATION: Protein N-terminal methyltransferase activity is
CC inhibited by GTP and GDP. {ECO:0000269|PubMed:30143613}.
CC -!- SUBUNIT: Forms a tripartite complex containing GAB1, METTL13 and SPRY2
CC (PubMed:29408807). Within the complex interacts with GAB1 and SPRY2
CC (PubMed:29408807). {ECO:0000269|PubMed:29408807}.
CC -!- INTERACTION:
CC Q8N6R0; Q86V38: ATN1; NbExp=3; IntAct=EBI-1053295, EBI-11954292;
CC Q8N6R0; P02489: CRYAA; NbExp=3; IntAct=EBI-1053295, EBI-6875961;
CC Q8N6R0; Q92876: KLK6; NbExp=3; IntAct=EBI-1053295, EBI-2432309;
CC Q8N6R0; P09012: SNRPA; NbExp=3; IntAct=EBI-1053295, EBI-607085;
CC Q8N6R0; Q9NVV9: THAP1; NbExp=4; IntAct=EBI-1053295, EBI-741515;
CC Q8N6R0; Q12933: TRAF2; NbExp=3; IntAct=EBI-1053295, EBI-355744;
CC Q8N6R0; Q8N1B4: VPS52; NbExp=3; IntAct=EBI-1053295, EBI-2799833;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27659353}. Nucleus
CC {ECO:0000269|PubMed:27659353}. Mitochondrion
CC {ECO:0000269|PubMed:27659353}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q8N6R0-5; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N6R0-4; Sequence=VSP_013922;
CC Name=3;
CC IsoId=Q8N6R0-3; Sequence=VSP_013919;
CC Name=4;
CC IsoId=Q8N6R0-1; Sequence=VSP_013920;
CC Name=5;
CC IsoId=Q8N6R0-2; Sequence=VSP_013919, VSP_013921;
CC -!- POLYMORPHISM: Genetic variants in METTL13 define the deafness modifier
CC locus DFNB26M [MIM:605429]. The DFNB26M phenotype is characterized by
CC normal hearing despite the presence of homozygosity for a causative
CC deafness mutation in the GAB1 gene. {ECO:0000269|PubMed:29408807}.
CC -!- DISEASE: Note=METTL13 unregulation may be involved in tumorigenesis.
CC High METTL13 expression has been observed in pancreatic and lung cancer
CC tissues, correlates with overexpression of dimethylated elongation
CC factor 1-alpha and is associated with poor clinical outcome. The
CC disease mechanism involves dysregulation of mRNA translation and
CC enhanced protein synthesis to sustain growth of malignant cells.
CC {ECO:0000269|PubMed:30612740}.
CC -!- MISCELLANEOUS: Present in the circulating blood plasma of cancer
CC patients, particularly in ovarian and non-small cell lung cancer
CC patients, may potentially be used as a biomarker (PubMed:27659353).
CC Acts as a tumor suppressor in bladder cancer suppressing cell migration
CC and invasion (PubMed:26763933). Reduced expression is seen in later
CC stages of the disease (PubMed:26763933). {ECO:0000269|PubMed:26763933,
CC ECO:0000269|PubMed:27659353}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74882.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD97213.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL049669; CAB41243.1; -; mRNA.
DR EMBL; AB020666; BAA74882.2; ALT_INIT; mRNA.
DR EMBL; AF132936; AAD27711.1; -; mRNA.
DR EMBL; AK027621; BAB55240.1; -; mRNA.
DR EMBL; AK074552; BAC11055.1; -; mRNA.
DR EMBL; AK291740; BAF84429.1; -; mRNA.
DR EMBL; AK223493; BAD97213.1; ALT_INIT; mRNA.
DR EMBL; AL031864; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006814; AAH06814.1; -; mRNA.
DR EMBL; BC029083; AAH29083.1; -; mRNA.
DR CCDS; CCDS1299.1; -. [Q8N6R0-5]
DR CCDS; CCDS1300.1; -. [Q8N6R0-3]
DR CCDS; CCDS30936.1; -. [Q8N6R0-1]
DR RefSeq; NP_001007240.1; NM_001007239.1. [Q8N6R0-1]
DR RefSeq; NP_055770.1; NM_014955.2. [Q8N6R0-3]
DR RefSeq; NP_057019.3; NM_015935.4. [Q8N6R0-5]
DR PDB; 5WCJ; X-ray; 1.70 A; A=470-699.
DR PDBsum; 5WCJ; -.
DR AlphaFoldDB; Q8N6R0; -.
DR SMR; Q8N6R0; -.
DR BioGRID; 119632; 77.
DR IntAct; Q8N6R0; 21.
DR MINT; Q8N6R0; -.
DR STRING; 9606.ENSP00000354920; -.
DR GlyGen; Q8N6R0; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q8N6R0; -.
DR PhosphoSitePlus; Q8N6R0; -.
DR BioMuta; METTL13; -.
DR DMDM; 67461056; -.
DR EPD; Q8N6R0; -.
DR jPOST; Q8N6R0; -.
DR MassIVE; Q8N6R0; -.
DR MaxQB; Q8N6R0; -.
DR PaxDb; Q8N6R0; -.
DR PeptideAtlas; Q8N6R0; -.
DR PRIDE; Q8N6R0; -.
DR ProteomicsDB; 72216; -. [Q8N6R0-5]
DR ProteomicsDB; 72217; -. [Q8N6R0-1]
DR ProteomicsDB; 72218; -. [Q8N6R0-2]
DR ProteomicsDB; 72219; -. [Q8N6R0-3]
DR ProteomicsDB; 72220; -. [Q8N6R0-4]
DR Antibodypedia; 20555; 85 antibodies from 19 providers.
DR DNASU; 51603; -.
DR Ensembl; ENST00000361735.4; ENSP00000354920.3; ENSG00000010165.20. [Q8N6R0-5]
DR Ensembl; ENST00000362019.7; ENSP00000355393.3; ENSG00000010165.20. [Q8N6R0-3]
DR Ensembl; ENST00000367737.9; ENSP00000356711.5; ENSG00000010165.20. [Q8N6R0-1]
DR GeneID; 51603; -.
DR KEGG; hsa:51603; -.
DR MANE-Select; ENST00000361735.4; ENSP00000354920.3; NM_015935.5; NP_057019.3.
DR UCSC; uc001ghz.4; human. [Q8N6R0-5]
DR CTD; 51603; -.
DR DisGeNET; 51603; -.
DR GeneCards; EEF1AKNMT; -.
DR HGNC; HGNC:24248; METTL13.
DR HPA; ENSG00000010165; Low tissue specificity.
DR MalaCards; EEF1AKNMT; -.
DR MIM; 605429; phenotype.
DR MIM; 617987; gene.
DR neXtProt; NX_Q8N6R0; -.
DR OpenTargets; ENSG00000010165; -.
DR VEuPathDB; HostDB:ENSG00000010165; -.
DR eggNOG; KOG2352; Eukaryota.
DR GeneTree; ENSGT00510000047399; -.
DR HOGENOM; CLU_010025_1_0_1; -.
DR InParanoid; Q8N6R0; -.
DR OMA; GEYCVEN; -.
DR PhylomeDB; Q8N6R0; -.
DR TreeFam; TF105906; -.
DR BRENDA; 2.1.1.244; 2681.
DR PathwayCommons; Q8N6R0; -.
DR SignaLink; Q8N6R0; -.
DR BioGRID-ORCS; 51603; 6 hits in 1076 CRISPR screens.
DR ChiTaRS; METTL13; human.
DR GeneWiki; KIAA0859; -.
DR GenomeRNAi; 51603; -.
DR Pharos; Q8N6R0; Tbio.
DR PRO; PR:Q8N6R0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8N6R0; protein.
DR Bgee; ENSG00000010165; Expressed in mucosa of transverse colon and 196 other tissues.
DR ExpressionAtlas; Q8N6R0; baseline and differential.
DR Genevisible; Q8N6R0; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 2.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08241; Methyltransf_11; 1.
DR SUPFAM; SSF53335; SSF53335; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Methyltransferase; Mitochondrion; Multifunctional enzyme; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..699
FT /note="eEF1A lysine and N-terminal methyltransferase"
FT /id="PRO_0000050779"
FT REGION 433..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..86
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013919"
FT VAR_SEQ 151..306
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_013920"
FT VAR_SEQ 289..505
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013921"
FT VAR_SEQ 643..699
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10810093"
FT /id="VSP_013922"
FT VARIANT 16
FT /note="Y -> C (found in a renal cell carcinoma sample;
FT somatic mutation; dbSNP:rs774565178)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064730"
FT VARIANT 105
FT /note="M -> V (in dbSNP:rs2232816)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_034040"
FT VARIANT 359
FT /note="M -> I (in dbSNP:rs2232819)"
FT /id="VAR_034041"
FT VARIANT 544
FT /note="R -> Q (acts as suppressor of deafness and is
FT associated with normal hearing in individuals homozygous
FT for a deafness-associated mutation in the GAB1 gene;
FT dbSNP:rs145666727)"
FT /evidence="ECO:0000269|PubMed:29408807"
FT /id="VAR_080810"
FT MUTAGEN 54
FT /note="V->A: Decreased eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 58
FT /note="G->R: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 59
FT /note="N->D: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 67
FT /note="Y->A: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 71
FT /note="Y->A: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 76
FT /note="N->D: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 115
FT /note="F->A: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 120..121
FT /note="DK->AA: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 156
FT /note="Y->A: Loss of eEF1A lysine methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:30612740"
FT MUTAGEN 524
FT /note="E->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT MUTAGEN 551
FT /note="D->A: Decreased activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT MUTAGEN 575
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT MUTAGEN 576
FT /note="V->A: Decreased activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT MUTAGEN 577
FT /note="D->A: Decreased activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT MUTAGEN 578
FT /note="S->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT MUTAGEN 647
FT /note="N->A: Decreased activity."
FT /evidence="ECO:0000269|PubMed:30143613"
FT CONFLICT 115
FT /note="F -> L (in Ref. 6; BAD97213)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="L -> S (in Ref. 6; BAD97213)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="H -> Q (in Ref. 5; BAB55240)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="T -> F (in Ref. 5; BAC11055)"
FT /evidence="ECO:0000305"
FT HELIX 472..479
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 480..483
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 487..492
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 495..500
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 506..514
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 518..525
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 527..536
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 545..550
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 552..560
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 563..565
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 569..574
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 590..593
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 595..603
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 605..616
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 620..633
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 636..641
FT /evidence="ECO:0007829|PDB:5WCJ"
FT STRAND 648..654
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 656..658
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 662..677
FT /evidence="ECO:0007829|PDB:5WCJ"
FT HELIX 689..692
FT /evidence="ECO:0007829|PDB:5WCJ"
SQ SEQUENCE 699 AA; 78768 MW; 14F80A4570047DBB CRC64;
MNLLPKSSRE FGSVDYWEKF FQQRGKKAFE WYGTYLELCG VLHKYIKPRE KVLVIGCGNS
ELSEQLYDVG YRDIVNIDIS EVVIKQMKEC NATRRPQMSF LKMDMTQMEF PDASFQVVLD
KGTLDAVLTD EEEKTLQQVD RMLAEVGRVL QVGGRYLCIS LAQAHILKKA VGHFSREGWM
VRVHQVANSQ DQVLEAEPQF SLPVFAFIMT KFRPVPGSAL QIFELCAQEQ RKPVRLESAE
RLAEAVQERQ QYAWLCSQLR RKARLGSVSL DLCDGDTGEP RYTLHVVDSP TVKPSRDNHF
AIFIIPQGRE TEWLFGMDEG RKQLAASAGF RRLITVALHR GQQYESMDHI QAELSARVME
LAPAGMPTQQ QVPFLSVGGD IGVRTVQHQD CSPLSGDYVI EDVQGDDKRY FRRLIFLSNR
NVVQSEARLL KDVSHKAQKK RKKDRKKQRP ADAEDLPAAP GQSIDKSYLC CEHHKAMIAG
LALLRNPELL LEIPLALLVV GLGGGSLPLF VHDHFPKSCI DAVEIDPSML EVATQWFGFS
QSDRMKVHIA DGLDYIASLA GGGEARPCYD VIMFDVDSKD PTLGMSCPPP AFVEQSFLQK
VKSILTPEGV FILNLVCRDL GLKDSVLAGL KAVFPLLYVR RIEGEVNEIL FCQLHPEQKL
ATPELLETAQ ALERTLRKPG RGWDDTYVLS DMLKTVKIV
