EFNMT_MOUSE
ID EFNMT_MOUSE Reviewed; 698 AA.
AC Q91YR5; Q3TF24; Q3TFY3; Q69ZX4; Q8BWN2; Q8BX81;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=eEF1A lysine and N-terminal methyltransferase {ECO:0000312|MGI:MGI:1918699};
DE Short=eEF1A-KNMT {ECO:0000250|UniProtKB:Q8N6R0};
DE AltName: Full=Methyltransferase-like protein 13 {ECO:0000250|UniProtKB:Q8N6R0};
DE Includes:
DE RecName: Full=eEF1A lysine methyltransferase {ECO:0000250|UniProtKB:Q8N6R0};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q8N6R0};
DE Includes:
DE RecName: Full=eEF1A N-terminal methyltransferase {ECO:0000250|UniProtKB:Q8N6R0};
DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q8N6R0};
GN Name=Mettl13 {ECO:0000303|PubMed:29408807};
GN Synonyms=EEF1AKNMT {ECO:0000312|MGI:MGI:1918699},
GN FEAT {ECO:0000303|PubMed:27659353};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Head, Heart, Kidney, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP PROTEIN SEQUENCE OF 2-9, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
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 [7]
RP TISSUE SPECIFICITY.
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).
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 (By similarity). Via its C-terminus, methylates EEF1A1 and
CC EEF1A2 at the N-terminal residue 'Gly-2' (By similarity). Via its N-
CC terminus dimethylates EEF1A1 and EEF1A2 at residue 'Lys-55' (By
CC similarity). Has no activity towards core histones H2A, H2B, H3 and H4
CC (By similarity). Negatively regulates cell proliferation at G1/S
CC transition via transcriptional suppression of cell cycle regulatory
CC genes such as CDK4 and CDK6 (By similarity).
CC {ECO:0000250|UniProtKB:Q8N6R0}.
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:0000250|UniProtKB:Q8N6R0};
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:0000250|UniProtKB:Q8N6R0};
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:0000250|UniProtKB:Q8N6R0};
CC -!- SUBUNIT: Forms a tripartite complex containing GAB1, METTL13 and SPRY2
CC (By similarity). Within the complex interacts with GAB1 and SPRY2 (By
CC similarity). {ECO:0000250|UniProtKB:Q8N6R0}.
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=3;
CC Name=1;
CC IsoId=Q91YR5-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91YR5-1; Sequence=VSP_013925, VSP_013926;
CC Name=3;
CC IsoId=Q91YR5-2; Sequence=VSP_013923, VSP_013924;
CC -!- TISSUE SPECIFICITY: Expressed in the inner ear (at protein level)
CC (PubMed:29408807). Expression is detected in the cochlear duct, spiral
CC limbus region, efferent and afferent nerves, and in spiral ganglion
CC neurons (at protein level) (PubMed:29408807).
CC {ECO:0000269|PubMed:29408807}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32322.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK048636; BAC33403.1; -; mRNA.
DR EMBL; AK050492; BAC34288.1; -; mRNA.
DR EMBL; AK146751; BAE27408.1; -; mRNA.
DR EMBL; AK168959; BAE40765.1; -; mRNA.
DR EMBL; AK169319; BAE41074.1; -; mRNA.
DR EMBL; AK173044; BAD32322.1; ALT_INIT; mRNA.
DR EMBL; BC014872; AAH14872.1; -; mRNA.
DR CCDS; CCDS15420.1; -. [Q91YR5-3]
DR RefSeq; NP_659126.1; NM_144877.1. [Q91YR5-3]
DR AlphaFoldDB; Q91YR5; -.
DR SMR; Q91YR5; -.
DR BioGRID; 214715; 1.
DR STRING; 10090.ENSMUSP00000028017; -.
DR iPTMnet; Q91YR5; -.
DR PhosphoSitePlus; Q91YR5; -.
DR EPD; Q91YR5; -.
DR MaxQB; Q91YR5; -.
DR PaxDb; Q91YR5; -.
DR PeptideAtlas; Q91YR5; -.
DR PRIDE; Q91YR5; -.
DR ProteomicsDB; 295933; -. [Q91YR5-3]
DR ProteomicsDB; 295934; -. [Q91YR5-1]
DR ProteomicsDB; 295935; -. [Q91YR5-2]
DR Antibodypedia; 20555; 85 antibodies from 19 providers.
DR DNASU; 71449; -.
DR Ensembl; ENSMUST00000028017; ENSMUSP00000028017; ENSMUSG00000026694. [Q91YR5-3]
DR GeneID; 71449; -.
DR KEGG; mmu:71449; -.
DR UCSC; uc007dgh.1; mouse. [Q91YR5-3]
DR UCSC; uc007dgi.1; mouse. [Q91YR5-1]
DR UCSC; uc007dgj.1; mouse. [Q91YR5-2]
DR CTD; 71449; -.
DR MGI; MGI:1918699; Eef1aknmt.
DR VEuPathDB; HostDB:ENSMUSG00000026694; -.
DR eggNOG; KOG2352; Eukaryota.
DR GeneTree; ENSGT00510000047399; -.
DR HOGENOM; CLU_010025_1_0_1; -.
DR InParanoid; Q91YR5; -.
DR OMA; GEYCVEN; -.
DR OrthoDB; 912165at2759; -.
DR PhylomeDB; Q91YR5; -.
DR TreeFam; TF105906; -.
DR BioGRID-ORCS; 71449; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Eef1aknmt; mouse.
DR PRO; PR:Q91YR5; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q91YR5; protein.
DR Bgee; ENSMUSG00000026694; Expressed in lumbar dorsal root ganglion and 211 other tissues.
DR ExpressionAtlas; Q91YR5; baseline and differential.
DR Genevisible; Q91YR5; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA: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; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS: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 Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Methyltransferase; Mitochondrion; Multifunctional enzyme; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..698
FT /note="eEF1A lysine and N-terminal methyltransferase"
FT /id="PRO_0000050780"
FT REGION 431..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6R0"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N6R0"
FT VAR_SEQ 305..318
FT /note="IPQGRETEWLFGME -> SELGLLRLSLEGLS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013923"
FT VAR_SEQ 319..698
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013924"
FT VAR_SEQ 374..377
FT /note="FLSV -> NSDL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013925"
FT VAR_SEQ 378..698
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013926"
FT CONFLICT 453
FT /note="T -> A (in Ref. 1; BAE41074)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 698 AA; 78757 MW; CAF0DA3A4049507A CRC64;
MNLLPKSSKE FGSADYWEKF FQQRGKTAFE WYGTYLELCE VLHKYIKPKE KVLVIGCGNS
ELSEQLYDVG YQDIVNIDIS EVVIKQMKER NGSRRPHMSF LKMDMTQLEF PDATFQVVLD
KGTLDAVLTD EEEVTLRQVD RMLAEVGRVL QVGGRYLCIS LAQAHILKKA VGHFSREGWM
VRAHQVASSQ DRVSEAEPRF SLPVFAFVMT KFRPVPGSAL QIFELCTQEQ GKPVRLESAD
QLAEAVRERQ YYAWLCSQLR RKAGLGSVSL DLCSGDTGEP RYTLHVVDNP AVKPSRDNHF
AIFIIPQGRE TEWLFGMEEG RKQLAASAGF RRLVTVALHR GQRYAGMESI QAELSARVME
LAPAGLPPQQ QVPFLSVGGD IGVRTVQHQD HSALSGDYVI EDVQGEDRWY FRRLIFLSNR
NVVQSEARLL KDTSHRAQKK RKKDRKKQRP ADTSEDFPPA PGQSIDKSYL CCEHHKAMVA
GLALLRNPEL LLETPLTLLV VGLGGGSLPL FVHDHFPKSR IDAVEIDPTM LEVATQWFGF
SQSDRMKVHI ADGLDYITSL AGEAPPHYDV IMFDVDSKDP TLGMSCPPPA FVDQVFLQKV
KSILCHDGVF ILNLVCRDVR LKDSVLAGLK AAFPLLYVRR IEGEVNEILF CQLHPEQKLA
TPELLEMAQV LERTLRKPGQ GWDDTYVLSD MLKTVKIV
