EFMT4_HUMAN
ID EFMT4_HUMAN Reviewed; 255 AA.
AC P0DPD7; A5PLK8; O60344; Q6NTG7; Q6UW36; Q8NFD7; Q96NX3; Q96NX4; Q9BRZ8;
DT 28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 28.
DE RecName: Full=EEF1A lysine methyltransferase 4 {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:28520920};
GN Name=EEF1AKMT4 {ECO:0000312|HGNC:HGNC:53611};
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 GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TYR-101.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-101.
RC TISSUE=Lung, and Ovary;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [5]
RP FUNCTION, MUTAGENESIS OF ASP-88; GLU-129; LYS-130; THR-132; LEU-133 AND
RP ASP-134, AND CATALYTIC ACTIVITY.
RX PubMed=28520920; DOI=10.1093/nar/gkx432;
RA Jakobsson M.E., Malecki J., Nilges B.S., Moen A., Leidel S.A., Falnes P.O.;
RT "Methylation of human eukaryotic elongation factor alpha (eEF1A) by a
RT member of a novel protein lysine methyltransferase family modulates mRNA
RT translation.";
RL Nucleic Acids Res. 45:8239-8254(2017).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 19-161 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE.
RX PubMed=19089949; DOI=10.1002/prot.22299;
RA Tempel W., Wu H., Dombrovsky L., Zeng H., Loppnau P., Zhu H.,
RA Plotnikov A.N., Bochkarev A.;
RT "An intact SAM-dependent methyltransferase fold is encoded by the human
RT endothelin-converting enzyme-2 gene.";
RL Proteins 74:789-793(2009).
CC -!- FUNCTION: Protein-lysine methyltransferase that efficiently catalyzes
CC three successive methylations on 'Lys-36' in eukaryotic translation
CC elongation factor 1 alpha (EEF1A1 or EEF1A2).
CC {ECO:0000269|PubMed:28520920}.
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:28520920};
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:28520920};
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:28520920};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=EEF1AKMT4-1;
CC IsoId=P0DPD7-4, O60344-4;
CC Sequence=Displayed;
CC Name=EEF1AKMT4-ECE2-1; Synonyms=ECE-2A;
CC IsoId=P0DPD8-1, O60344-1;
CC Sequence=External;
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; AC061705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC078797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78277.1; -; Genomic_DNA.
DR EMBL; BC005835; AAH05835.1; -; mRNA.
DR EMBL; BC012449; AAH12449.1; -; mRNA.
DR EMBL; BC069005; AAH69005.1; -; mRNA.
DR CCDS; CCDS3255.1; -.
DR RefSeq; NP_115707.2; NM_032331.3. [P0DPD7-4]
DR PDB; 2PXX; X-ray; 1.30 A; A=19-231.
DR PDBsum; 2PXX; -.
DR AlphaFoldDB; P0DPD7; -.
DR SMR; P0DPD7; -.
DR GlyGen; P0DPD7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P0DPD7; -.
DR PhosphoSitePlus; P0DPD7; -.
DR EPD; P0DPD7; -.
DR jPOST; P0DPD7; -.
DR MassIVE; P0DPD7; -.
DR MaxQB; P0DPD7; -.
DR PeptideAtlas; P0DPD7; -.
DR PRIDE; P0DPD7; -.
DR Ensembl; ENST00000324557.9; ENSP00000314295.5; ENSG00000284753.2. [P0DPD7-4]
DR GeneID; 110599564; -.
DR KEGG; hsa:110599564; -.
DR MANE-Select; ENST00000324557.9; ENSP00000314295.5; NM_032331.4; NP_115707.2.
DR CTD; 110599564; -.
DR DisGeNET; 110599564; -.
DR GeneCards; EEF1AKMT4; -.
DR HGNC; HGNC:53611; EEF1AKMT4.
DR HPA; ENSG00000284753; Low tissue specificity.
DR MIM; 610145; gene.
DR neXtProt; NX_P0DPD7; -.
DR VEuPathDB; HostDB:ENSG00000284753; -.
DR GeneTree; ENSGT00940000164140; -.
DR OMA; INMFHEE; -.
DR PathwayCommons; P0DPD7; -.
DR Pharos; P0DPD7; Tdark.
DR PRO; PR:P0DPD7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR Bgee; ENSG00000284753; Expressed in left testis and 102 other tissues.
DR GO; GO:0008168; F:methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08241; Methyltransf_11; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Methyltransferase; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..255
FT /note="EEF1A lysine methyltransferase 4"
FT /id="PRO_0000443290"
FT MOTIF 129..134
FT /note="Required for methyltransferase activity"
FT BINDING 26
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT BINDING 30
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT BINDING 41
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT BINDING 66
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT BINDING 88..89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT BINDING 113..114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT BINDING 130
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:19089949,
FT ECO:0007744|PDB:2PXX"
FT MOD_RES 39
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT VARIANT 101
FT /note="H -> Y (in dbSNP:rs7633387)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_047752"
FT MUTAGEN 88
FT /note="D->A: Abolishes methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:28520920"
FT MUTAGEN 129
FT /note="E->A: Abolishes protein-lysine N-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:28520920"
FT MUTAGEN 130
FT /note="K->A: Abolishes protein-lysine N-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:28520920"
FT MUTAGEN 132
FT /note="T->A: Reduces protein-lysine N-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:28520920"
FT MUTAGEN 133
FT /note="L->A: Reduces protein-lysine N-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:28520920"
FT MUTAGEN 134
FT /note="D->A: Abolishes protein-lysine N-methyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:28520920"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 23..29
FT /evidence="ECO:0007829|PDB:2PXX"
FT TURN 30..35
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 45..52
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 72..78
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 91..100
FT /evidence="ECO:0007829|PDB:2PXX"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 124..131
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 132..136
FT /evidence="ECO:0007829|PDB:2PXX"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 148..164
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 165..176
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 179..186
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:2PXX"
FT STRAND 206..213
FT /evidence="ECO:0007829|PDB:2PXX"
FT HELIX 219..225
FT /evidence="ECO:0007829|PDB:2PXX"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:2PXX"
SQ SEQUENCE 255 AA; 28306 MW; 39389C81C0798805 CRC64;
MASPGAGRAP PELPERNCGY REVEYWDQRY QGAADSAPYD WFGDFSSFRA LLEPELRPED
RILVLGCGNS ALSYELFLGG FPNVTSVDYS SVVVAAMQAR HAHVPQLRWE TMDVRKLDFP
SASFDVVLEK GTLDALLAGE RDPWTVSSEG VHTVDQVLSE VSRVLVPGGR FISMTSAAPH
FRTRHYAQAY YGWSLRHATY GSGFHFHLYL MHKGGKLSVA QLALGAQILS PPRPPTSPCF
LQDSDHEDFL SAIQL
