EF2KT_HUMAN
ID EF2KT_HUMAN Reviewed; 330 AA.
AC Q96G04; D3DUF0; Q96S85;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Protein-lysine N-methyltransferase EEF2KMT {ECO:0000305};
DE EC=2.1.1.- {ECO:0000269|PubMed:25231979};
DE AltName: Full=eEF2-lysine methyltransferase;
DE Short=eEF2-KMT;
GN Name=EEF2KMT {ECO:0000312|HGNC:HGNC:32221};
GN Synonyms=FAM86A {ECO:0000312|HGNC:HGNC:32221}; ORFNames=SB153;
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 2).
RA Li N., Zhang M., Wan T., Zhang W., Cao X.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-272.
RA Mural R.J., Istrail S., Sutton 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] (ISOFORM 1), AND VARIANT ASP-272.
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 [4]
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 [5]
RP INTERACTION WITH FAM86B2 AND FAM86C1P, 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, AND CATALYTIC ACTIVITY.
RX PubMed=25231979; DOI=10.1074/jbc.m114.601658;
RA Davydova E., Ho A.Y., Malecki J., Moen A., Enserink J.M., Jakobsson M.E.,
RA Loenarz C., Falnes P.O.;
RT "Identification and characterization of a novel evolutionarily conserved
RT lysine-specific methyltransferase targeting eukaryotic translation
RT elongation factor 2 (eEF2).";
RL J. Biol. Chem. 289:30499-30510(2014).
CC -!- FUNCTION: Catalyzes the trimethylation of eukaryotic elongation factor
CC 2 (EEF2) on 'Lys-525'. {ECO:0000269|PubMed:25231979}.
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:25231979};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54193;
CC Evidence={ECO:0000305|PubMed:25231979};
CC -!- SUBUNIT: Interacts with FAM86B2 and FAM86C1P.
CC {ECO:0000269|PubMed:23349634}.
CC -!- INTERACTION:
CC Q96G04; P00492: HPRT1; NbExp=3; IntAct=EBI-747840, EBI-748210;
CC Q96G04; Q13099: IFT88; NbExp=3; IntAct=EBI-747840, EBI-347427;
CC Q96G04; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-747840, EBI-3437878;
CC Q96G04; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-747840, EBI-739832;
CC Q96G04; P51843: NR0B1; NbExp=3; IntAct=EBI-747840, EBI-946109;
CC Q96G04; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-747840, EBI-79165;
CC Q96G04; P31321: PRKAR1B; NbExp=3; IntAct=EBI-747840, EBI-2805516;
CC Q96G04; Q9NRG1: PRTFDC1; NbExp=8; IntAct=EBI-747840, EBI-739759;
CC Q96G04; Q15645: TRIP13; NbExp=3; IntAct=EBI-747840, EBI-358993;
CC Q96G04; O14771: ZNF213; NbExp=3; IntAct=EBI-747840, EBI-12838388;
CC Q96G04; P13682: ZNF35; NbExp=3; IntAct=EBI-747840, EBI-11041653;
CC Q96G04; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-747840, EBI-4395669;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23349634}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96G04-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96G04-2; Sequence=VSP_017097;
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. EEF2KMT family. {ECO:0000305}.
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DR EMBL; AY037162; AAK67640.1; -; mRNA.
DR EMBL; CH471112; EAW85235.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85236.1; -; Genomic_DNA.
DR EMBL; BC010084; AAH10084.1; -; mRNA.
DR CCDS; CCDS10529.1; -. [Q96G04-1]
DR CCDS; CCDS10530.1; -. [Q96G04-2]
DR RefSeq; NP_001275958.1; NM_001289029.1.
DR RefSeq; NP_958802.1; NM_201400.3. [Q96G04-1]
DR RefSeq; NP_963892.1; NM_201598.3. [Q96G04-2]
DR AlphaFoldDB; Q96G04; -.
DR SMR; Q96G04; -.
DR BioGRID; 128213; 28.
DR IntAct; Q96G04; 16.
DR STRING; 9606.ENSP00000398502; -.
DR iPTMnet; Q96G04; -.
DR PhosphoSitePlus; Q96G04; -.
DR BioMuta; EEF2KMT; -.
DR DMDM; 85700958; -.
DR EPD; Q96G04; -.
DR jPOST; Q96G04; -.
DR MassIVE; Q96G04; -.
DR MaxQB; Q96G04; -.
DR PaxDb; Q96G04; -.
DR PeptideAtlas; Q96G04; -.
DR PRIDE; Q96G04; -.
DR ProteomicsDB; 76581; -. [Q96G04-1]
DR ProteomicsDB; 76582; -. [Q96G04-2]
DR Antibodypedia; 55831; 63 antibodies from 12 providers.
DR DNASU; 196483; -.
DR Ensembl; ENST00000427587.9; ENSP00000398502.3; ENSG00000118894.15. [Q96G04-1]
DR Ensembl; ENST00000458008.8; ENSP00000389710.3; ENSG00000118894.15. [Q96G04-2]
DR GeneID; 196483; -.
DR KEGG; hsa:196483; -.
DR MANE-Select; ENST00000427587.9; ENSP00000398502.3; NM_201400.4; NP_958802.1.
DR UCSC; uc002cyo.4; human. [Q96G04-1]
DR CTD; 196483; -.
DR DisGeNET; 196483; -.
DR GeneCards; EEF2KMT; -.
DR HGNC; HGNC:32221; EEF2KMT.
DR HPA; ENSG00000118894; Low tissue specificity.
DR MIM; 615263; gene.
DR neXtProt; NX_Q96G04; -.
DR OpenTargets; ENSG00000118894; -.
DR PharmGKB; PA142671858; -.
DR VEuPathDB; HostDB:ENSG00000118894; -.
DR eggNOG; KOG2497; Eukaryota.
DR GeneTree; ENSGT00510000047003; -.
DR HOGENOM; CLU_038942_0_0_1; -.
DR InParanoid; Q96G04; -.
DR OMA; TGFFHST; -.
DR OrthoDB; 958308at2759; -.
DR PhylomeDB; Q96G04; -.
DR TreeFam; TF326304; -.
DR PathwayCommons; Q96G04; -.
DR Reactome; R-HSA-8876725; Protein methylation.
DR SignaLink; Q96G04; -.
DR BioGRID-ORCS; 196483; 433 hits in 1010 CRISPR screens.
DR ChiTaRS; EEF2KMT; human.
DR GenomeRNAi; 196483; -.
DR Pharos; Q96G04; Tdark.
DR PRO; PR:Q96G04; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q96G04; protein.
DR Bgee; ENSG00000118894; Expressed in mucosa of transverse colon and 109 other tissues.
DR ExpressionAtlas; Q96G04; baseline and differential.
DR Genevisible; Q96G04; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0018023; P:peptidyl-lysine trimethylation; IDA:UniProtKB.
DR GO; GO:0006479; P:protein methylation; TAS:Reactome.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR029426; FAM86_N.
DR InterPro; IPR019410; Methyltransf_16.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR14614; PTHR14614; 1.
DR Pfam; PF14904; FAM86; 1.
DR Pfam; PF10294; Methyltransf_16; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Methyltransferase;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..330
FT /note="Protein-lysine N-methyltransferase EEF2KMT"
FT /id="PRO_0000076218"
FT BINDING 139
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 165..167
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 228
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT BINDING 247
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9H867"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 81..114
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_017097"
FT VARIANT 123
FT /note="S -> C (in dbSNP:rs9673733)"
FT /id="VAR_033854"
FT VARIANT 230
FT /note="V -> I (in dbSNP:rs148557961)"
FT /id="VAR_067704"
FT VARIANT 270
FT /note="R -> W (in dbSNP:rs3204207)"
FT /id="VAR_060160"
FT VARIANT 272
FT /note="H -> D (in dbSNP:rs12928528)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_067705"
FT VARIANT 329
FT /note="T -> I (in dbSNP:rs760584474)"
FT /id="VAR_067706"
SQ SEQUENCE 330 AA; 36915 MW; 1C1B37B9F6D2EE52 CRC64;
MAPEENAGTE LLLQSFERRF LAARTLRSFP WQSLEAKLRD SSDSELLRDI LHKTVKHPVC
VKHPPSVKYA RCFLSELIKK HEAVHTEPLD ELYEALAETL MAKESTQGHR SYLLPSGGSV
TLSESTAIIS YGTTGLVTWD AALYLAEWAI ENPAVFTNRT VLELGSGAGL TGLAICKMCR
PRAYIFSDCH SRVLEQLRGN VLLNGLSLEA DITAKLDSPR VTVAQLDWDV ATVHQLSAFQ
PDVVIAADVL YCPEAIMSLV GVLRRLAACR EHQRAPEVYV AFTVRNPETC QLFTTELGRA
GIRWEVEPRH EQKLFPYEEH LEMAMLNLTL
