EFMT3_HUMAN
ID EFMT3_HUMAN Reviewed; 226 AA.
AC Q96AZ1; Q9H749; Q9Y3W2;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=EEF1A lysine methyltransferase 3 {ECO:0000312|HGNC:HGNC:24936};
DE EC=2.1.1.- {ECO:0000269|PubMed:28108655, ECO:0000269|PubMed:28663172};
DE AltName: Full=Hepatocellular carcinoma-associated antigen 557a;
DE AltName: Full=Methyltransferase-like protein 21B;
DE AltName: Full=Protein-lysine methyltransferase METTL21B;
DE AltName: Full=eEF1A-KMT3 {ECO:0000303|PubMed:28108655, ECO:0000303|PubMed:28663172};
GN Name=EEF1AKMT3 {ECO:0000312|HGNC:HGNC:24936};
GN Synonyms=FAM119B, HCA557A {ECO:0000303|Ref.1},
GN METTL21B {ECO:0000303|PubMed:28108655};
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 [MRNA] (ISOFORM 1).
RA Dong X.-Y., Chen W.-F.;
RT "HCA557a, a transcription factor associated with hepatocellular
RT carcinoma.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Colon;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [5]
RP INTERACTION WITH HSP70 FAMILY MEMBERS; TCP-1 CHAPERONIN FAMILY MEMBERS;
RP HSPD1; STIP1 AND TUBULIN, AND SUBCELLULAR LOCATION.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine methyltransferases
RT preferentially interact with molecular chaperones to regulate their
RT activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=28108655; DOI=10.1093/nar/gkx002;
RA Malecki J., Aileni V.K., Ho A.Y., Schwarz J., Moen A., Soerensen V.,
RA Nilges B.S., Jakobsson M.E., Leidel S.A., Falnes P.O.;
RT "The novel lysine specific methyltransferase METTL21B affects mRNA
RT translation through inducible and dynamic methylation of Lys-165 in human
RT eukaryotic elongation factor 1 alpha (eEF1A).";
RL Nucleic Acids Res. 45:4370-4389(2017).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28663172; DOI=10.1074/mcp.m116.066308;
RA Hamey J.J., Wienert B., Quinlan K.G.R., Wilkins M.R.;
RT "METTL21B Is a Novel Human Lysine Methyltransferase of Translation
RT Elongation Factor 1A: Discovery by CRISPR/Cas9 Knockout.";
RL Mol. Cell. Proteomics 16:2229-2242(2017).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human methyltransferase-like protein 21B.";
RL Submitted (JUN-2014) to the PDB data bank.
CC -!- FUNCTION: Protein-lysine methyltransferase that selectively mono-,
CC di- and trimethylates 'Lys-165' of the translation elongation factors
CC EEF1A1 and EEF1A2 in an aminoacyl-tRNA and GTP-dependent manner. EEF1A1
CC methylation by EEF1AKMT3 is dynamic as well as inducible by stress
CC conditions, such as ER-stress, and plays a regulatory role on mRNA
CC translation. {ECO:0000269|PubMed:28108655,
CC ECO:0000269|PubMed:28663172}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl-[protein] + 3 S-adenosyl-L-methionine = 3 H(+) +
CC N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:54192, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:13826, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961;
CC Evidence={ECO:0000269|PubMed:28108655, ECO:0000269|PubMed:28663172};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54193;
CC Evidence={ECO:0000305|PubMed:28108655};
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:28108655, ECO:0000269|PubMed:28663172};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51737;
CC Evidence={ECO:0000305|PubMed:28108655};
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:28108655, ECO:0000269|PubMed:28663172};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54197;
CC Evidence={ECO:0000305|PubMed:28108655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:54200, Rhea:RHEA-COMP:13826, Rhea:RHEA-
CC COMP:13827, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61961, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:28108655, ECO:0000269|PubMed:28663172};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54201;
CC Evidence={ECO:0000305|PubMed:28108655};
CC -!- SUBUNIT: Interacts with members of the heat shock protein 70 and 90
CC families and of the TCP-1 chaperonin family, as well as with HSPD1,
CC STIP1 and tubulin; at least some of these proteins may be methylation
CC substrates. {ECO:0000269|PubMed:23349634}.
CC -!- INTERACTION:
CC Q96AZ1; Q60I27: ALS2CL; NbExp=3; IntAct=EBI-12108304, EBI-12078276;
CC Q96AZ1; O15481: MAGEB4; NbExp=3; IntAct=EBI-12108304, EBI-751857;
CC Q96AZ1; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-12108304, EBI-10699187;
CC Q96AZ1; Q08AM6: VAC14; NbExp=3; IntAct=EBI-12108304, EBI-2107455;
CC Q96AZ1; Q15915: ZIC1; NbExp=3; IntAct=EBI-12108304, EBI-11963196;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23349634,
CC ECO:0000269|PubMed:28108655}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:28108655}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96AZ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96AZ1-2; Sequence=VSP_026270, VSP_026271;
CC Name=3;
CC IsoId=Q96AZ1-3; Sequence=VSP_026268, VSP_026269;
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. METTL21
CC family. {ECO:0000305}.
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DR EMBL; AF455816; AAL66294.1; -; mRNA.
DR EMBL; AK024983; BAB15049.1; -; mRNA.
DR EMBL; AL050100; CAB43271.2; -; mRNA.
DR EMBL; BC016395; AAH16395.1; -; mRNA.
DR EMBL; BC099841; AAH99841.1; -; mRNA.
DR EMBL; BC103501; AAI03502.1; -; mRNA.
DR CCDS; CCDS31848.1; -. [Q96AZ1-2]
DR CCDS; CCDS8957.1; -. [Q96AZ1-1]
DR PIR; T08749; T08749.
DR RefSeq; NP_056248.2; NM_015433.2. [Q96AZ1-1]
DR RefSeq; NP_996797.1; NM_206914.1. [Q96AZ1-2]
DR PDB; 4QPN; X-ray; 1.25 A; A=1-226.
DR PDBsum; 4QPN; -.
DR AlphaFoldDB; Q96AZ1; -.
DR SMR; Q96AZ1; -.
DR BioGRID; 117403; 409.
DR IntAct; Q96AZ1; 5.
DR STRING; 9606.ENSP00000300209; -.
DR iPTMnet; Q96AZ1; -.
DR PhosphoSitePlus; Q96AZ1; -.
DR BioMuta; EEF1AKMT3; -.
DR DMDM; 74731178; -.
DR MassIVE; Q96AZ1; -.
DR MaxQB; Q96AZ1; -.
DR PaxDb; Q96AZ1; -.
DR PeptideAtlas; Q96AZ1; -.
DR PRIDE; Q96AZ1; -.
DR ProteomicsDB; 76022; -. [Q96AZ1-1]
DR Antibodypedia; 28949; 19 antibodies from 9 providers.
DR DNASU; 25895; -.
DR Ensembl; ENST00000300209.13; ENSP00000300209.8; ENSG00000123427.17. [Q96AZ1-1]
DR Ensembl; ENST00000333012.5; ENSP00000327425.5; ENSG00000123427.17. [Q96AZ1-2]
DR GeneID; 25895; -.
DR KEGG; hsa:25895; -.
DR MANE-Select; ENST00000300209.13; ENSP00000300209.8; NM_015433.3; NP_056248.2.
DR UCSC; uc001sqf.4; human. [Q96AZ1-1]
DR CTD; 25895; -.
DR DisGeNET; 25895; -.
DR GeneCards; EEF1AKMT3; -.
DR HGNC; HGNC:24936; EEF1AKMT3.
DR HPA; ENSG00000123427; Low tissue specificity.
DR MIM; 615258; gene.
DR neXtProt; NX_Q96AZ1; -.
DR OpenTargets; ENSG00000123427; -.
DR PharmGKB; PA145008445; -.
DR VEuPathDB; HostDB:ENSG00000123427; -.
DR eggNOG; KOG2793; Eukaryota.
DR GeneTree; ENSGT00940000161297; -.
DR HOGENOM; CLU_055721_4_0_1; -.
DR InParanoid; Q96AZ1; -.
DR OMA; HRDDKQN; -.
DR OrthoDB; 1494909at2759; -.
DR PhylomeDB; Q96AZ1; -.
DR TreeFam; TF313206; -.
DR PathwayCommons; Q96AZ1; -.
DR SignaLink; Q96AZ1; -.
DR BioGRID-ORCS; 25895; 26 hits in 1075 CRISPR screens.
DR GenomeRNAi; 25895; -.
DR Pharos; Q96AZ1; Tdark.
DR PRO; PR:Q96AZ1; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96AZ1; protein.
DR Bgee; ENSG00000123427; Expressed in body of pancreas and 149 other tissues.
DR ExpressionAtlas; Q96AZ1; baseline and differential.
DR Genevisible; Q96AZ1; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005694; C:chromosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB.
DR GO; GO:0008168; F:methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0018022; P:peptidyl-lysine methylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR019410; Methyltransf_16.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR14614; PTHR14614; 1.
DR Pfam; PF10294; Methyltransf_16; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..226
FT /note="EEF1A lysine methyltransferase 3"
FT /id="PRO_0000291850"
FT BINDING 57
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:4QPN"
FT BINDING 83..85
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:4QPN"
FT BINDING 104
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:4QPN"
FT BINDING 133
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:4QPN"
FT BINDING 150
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PDB:4QPN"
FT VAR_SEQ 1..71
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_026268"
FT VAR_SEQ 72..97
FT /note="VDFRGKKVIELGAGTGIVGILAALQG -> MRGACGHALSMSTMTPWESIKG
FT SSVR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_026269"
FT VAR_SEQ 98..149
FT /note="GDVTITDLPLALEQIQGNVQANVPAGGQAQVRALSWGIDHHVFPANYDLVLG
FT -> AYGLVRETEDDVIEQELWRGMRGACGHALSMSTMTPWESIKGSSVRGGCYHH (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_026270"
FT VAR_SEQ 150..226
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_026271"
FT VARIANT 28
FT /note="S -> L (in dbSNP:rs34913183)"
FT /id="VAR_032869"
FT STRAND 27..35
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 38..49
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 58..69
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 88..95
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 109..119
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:4QPN"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 159..169
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 170..181
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 188..193
FT /evidence="ECO:0007829|PDB:4QPN"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 200..208
FT /evidence="ECO:0007829|PDB:4QPN"
FT TURN 209..212
FT /evidence="ECO:0007829|PDB:4QPN"
FT STRAND 213..220
FT /evidence="ECO:0007829|PDB:4QPN"
SQ SEQUENCE 226 AA; 24911 MW; A73C4B00AF18B10B CRC64;
MADPGPDPES ESESVFPREV GLFADSYSEK SQFCFCGHVL TITQNFGSRL GVAARVWDAA
LSLCNYFESQ NVDFRGKKVI ELGAGTGIVG ILAALQGGDV TITDLPLALE QIQGNVQANV
PAGGQAQVRA LSWGIDHHVF PANYDLVLGA DIVYLEPTFP LLLGTLQHLC RPHGTIYLAS
KMRKEHGTES FFQHLLPQHF QLELAQRDED ENVNIYRARH REPRPA
