EF2K_HUMAN
ID EF2K_HUMAN Reviewed; 725 AA.
AC O00418; Q8N588;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Eukaryotic elongation factor 2 kinase;
DE Short=eEF-2 kinase;
DE Short=eEF-2K;
DE EC=2.7.11.20 {ECO:0000269|PubMed:11015200, ECO:0000269|PubMed:9144159};
DE AltName: Full=Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase;
GN Name=EEF2K;
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], FUNCTION, CATALYTIC ACTIVITY, AND VARIANT
RP ARG-361.
RC TISSUE=Glial tumor;
RX PubMed=9144159; DOI=10.1073/pnas.94.10.4884;
RA Ryazanov A.G., Ward M.D., Mendola C.E., Pavur K.S., Dorovkov M.V.,
RA Wiedmann M., Erdjument-Bromage H., Tempst P., Parmer T.G., Prostko C.R.,
RA Germino F.J., Hait W.N.;
RT "Identification of a new class of protein kinases represented by eukaryotic
RT elongation factor-2 kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:4884-4889(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-23 AND ARG-361.
RC TISSUE=Lymph;
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 CATALYTIC ACTIVITY, IDENTIFICATION OF THE CALMODULIN-BINDING REGION,
RP AUTOPHOSPHORYLATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11015200; DOI=10.1021/bi0007270;
RA Pavur K.S., Petrov A.N., Ryazanov A.G.;
RT "Mapping the functional domains of elongation factor-2 kinase.";
RL Biochemistry 39:12216-12224(2000).
RN [5]
RP PHOSPHORYLATION AT SER-359.
RX PubMed=11500363; DOI=10.1093/emboj/20.16.4360;
RA Knebel A., Morrice N., Cohen P.;
RT "A novel method to identify protein kinase substrates: eEF2 kinase is
RT phosphorylated and inhibited by SAPK4/p38delta.";
RL EMBO J. 20:4360-4369(2001).
RN [6]
RP PHOSPHORYLATION AT SER-366 BY RPS6KA1 AND RPS6KB1, AND MUTAGENESIS OF
RP SER-366.
RX PubMed=11500364; DOI=10.1093/emboj/20.16.4370;
RA Wang X., Li W., Williams M., Terada N., Alessi D.R., Proud C.G.;
RT "Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase.";
RL EMBO J. 20:4370-4379(2001).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [8]
RP FUNCTION, AND PHOSPHORYLATION AT SER-398.
RX PubMed=14709557; DOI=10.1074/jbc.m309773200;
RA Browne G.J., Finn S.G., Proud C.G.;
RT "Stimulation of the AMP-activated protein kinase leads to activation of
RT eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel
RT site, serine 398.";
RL J. Biol. Chem. 279:12220-12231(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-474, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-445, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP PHOSPHORYLATION AT SER-359.
RX PubMed=18337751; DOI=10.1038/emboj.2008.39;
RA Smith E.M., Proud C.G.;
RT "cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino
RT acid-dependent manner.";
RL EMBO J. 27:1005-1016(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-348; SER-470; SER-474 AND
RP SER-477, AND IDENTIFICATION BY 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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; THR-348; SER-445; SER-470
RP AND SER-474, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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 [17]
RP PHOSPHORYLATION AT SER-78.
RX PubMed=21112387; DOI=10.1016/j.cellsig.2010.11.011;
RA Perraud A.L., Zhao X., Ryazanov A.G., Schmitz C.;
RT "The channel-kinase TRPM7 regulates phosphorylation of the translational
RT factor eEF2 via eEF2-k.";
RL Cell. Signal. 23:586-593(2011).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-470, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP PHOSPHORYLATION AT SER-61; SER-66; SER-78; THR-348; THR-353; SER-366;
RP SER-445; SER-474 AND SER-491, AND MUTAGENESIS OF SER-78; THR-348 AND
RP SER-366.
RX PubMed=22216903; DOI=10.1042/bj20111530;
RA Pyr Dit Ruys S., Wang X., Smith E.M., Herinckx G., Hussain N., Rider M.H.,
RA Vertommen D., Proud C.G.;
RT "Identification of autophosphorylation sites in eukaryotic elongation
RT factor-2 kinase.";
RL Biochem. J. 442:681-692(2012).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18; SER-70; SER-72; SER-74;
RP SER-78; SER-243; THR-348; THR-353; SER-435; SER-445; SER-470; SER-474;
RP SER-477 AND SER-491, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27; THR-348; SER-445 AND
RP SER-474, AND 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 [23]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-23; ALA-75; MET-291; TRP-433 AND
RP HIS-609.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Threonine kinase that regulates protein synthesis by
CC controlling the rate of peptide chain elongation. Upon activation by a
CC variety of upstream kinases including AMPK or TRPM7, phosphorylates the
CC elongation factor EEF2 at a single site, renders it unable to bind
CC ribosomes and thus inactive. In turn, the rate of protein synthesis is
CC reduced. {ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:9144159}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[translation elongation factor 2] + ATP = [translation
CC elongation factor 2]-phosphate + ADP + H(+); Xref=Rhea:RHEA:21436,
CC Rhea:RHEA-COMP:11268, Rhea:RHEA-COMP:11269, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.20;
CC Evidence={ECO:0000269|PubMed:11015200, ECO:0000269|PubMed:9144159};
CC -!- ACTIVITY REGULATION: Undergoes calcium/calmodulin-dependent
CC intramolecular autophosphorylation, and this results in it becoming
CC partially calcium/calmodulin-independent. {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 uM for EEF2 {ECO:0000269|PubMed:11015200};
CC Vmax=4 nmol/min/mg enzyme {ECO:0000269|PubMed:11015200};
CC -!- SUBUNIT: Monomer or homodimer (Probable). Interacts with
CC Calmodulin/CALM1; this interaction is strictly required for
CC phosphorylation activity (PubMed:11015200).
CC {ECO:0000269|PubMed:11015200, ECO:0000305}.
CC -!- PTM: Autophosphorylated at multiple residues, Thr-348 being the major
CC site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-398
CC leading to EEF2K activation and protein synthesis inhibition.
CC Phosphorylated by TRPM7 at Ser-78 resulting in improved protein
CC stability, higher EE2F phosphorylated and subsequently reduced rate of
CC protein synthesis. Phosphorylation by other kinases such as CDK1 and
CC MAPK13 at Ser-359 or RPS6KA1 and RPS6KB1 at Ser-366 instead decrease
CC EEF2K activity and promote protein synthesis.
CC {ECO:0000269|PubMed:11015200, ECO:0000269|PubMed:11500363,
CC ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:14709557,
CC ECO:0000269|PubMed:18337751, ECO:0000269|PubMed:21112387,
CC ECO:0000269|PubMed:22216903}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Alpha-type
CC protein kinase family. {ECO:0000305}.
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DR EMBL; U93850; AAB58270.1; -; mRNA.
DR EMBL; AC009034; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032665; AAH32665.1; -; mRNA.
DR CCDS; CCDS10604.1; -.
DR RefSeq; NP_037434.1; NM_013302.3.
DR RefSeq; XP_005276554.1; XM_005276497.3.
DR RefSeq; XP_016878682.1; XM_017023193.1.
DR PDB; 5J8H; NMR; -; B=74-100.
DR PDB; 5KS5; NMR; -; A=627-725.
DR PDB; 6NX4; NMR; -; A=562-725.
DR PDB; 7SHQ; X-ray; 2.34 A; A=70-358, A=490-725.
DR PDBsum; 5J8H; -.
DR PDBsum; 5KS5; -.
DR PDBsum; 6NX4; -.
DR PDBsum; 7SHQ; -.
DR AlphaFoldDB; O00418; -.
DR SMR; O00418; -.
DR BioGRID; 118953; 55.
DR BioGRID; 3193665; 1.
DR ELM; O00418; -.
DR IntAct; O00418; 20.
DR MINT; O00418; -.
DR STRING; 9606.ENSP00000263026; -.
DR BindingDB; O00418; -.
DR ChEMBL; CHEMBL5026; -.
DR GuidetoPHARMACOLOGY; 2014; -.
DR GlyGen; O00418; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00418; -.
DR MetOSite; O00418; -.
DR PhosphoSitePlus; O00418; -.
DR BioMuta; EEF2K; -.
DR EPD; O00418; -.
DR jPOST; O00418; -.
DR MassIVE; O00418; -.
DR MaxQB; O00418; -.
DR PaxDb; O00418; -.
DR PeptideAtlas; O00418; -.
DR PRIDE; O00418; -.
DR ProteomicsDB; 47876; -.
DR Antibodypedia; 25835; 468 antibodies from 34 providers.
DR DNASU; 29904; -.
DR Ensembl; ENST00000263026.10; ENSP00000263026.5; ENSG00000103319.12.
DR GeneID; 29904; -.
DR KEGG; hsa:29904; -.
DR MANE-Select; ENST00000263026.10; ENSP00000263026.5; NM_013302.5; NP_037434.2.
DR UCSC; uc002dki.4; human.
DR CTD; 29904; -.
DR DisGeNET; 29904; -.
DR GeneCards; EEF2K; -.
DR HGNC; HGNC:24615; EEF2K.
DR HPA; ENSG00000103319; Tissue enhanced (skin).
DR MIM; 606968; gene.
DR neXtProt; NX_O00418; -.
DR OpenTargets; ENSG00000103319; -.
DR PharmGKB; PA134992891; -.
DR VEuPathDB; HostDB:ENSG00000103319; -.
DR eggNOG; ENOG502QVA3; Eukaryota.
DR GeneTree; ENSGT00940000157839; -.
DR HOGENOM; CLU_382143_0_0_1; -.
DR InParanoid; O00418; -.
DR OMA; LEAIITM; -.
DR OrthoDB; 741011at2759; -.
DR PhylomeDB; O00418; -.
DR TreeFam; TF316085; -.
DR BRENDA; 2.7.11.20; 2681.
DR PathwayCommons; O00418; -.
DR Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR SignaLink; O00418; -.
DR SIGNOR; O00418; -.
DR BioGRID-ORCS; 29904; 9 hits in 1112 CRISPR screens.
DR ChiTaRS; EEF2K; human.
DR GeneWiki; EEF2K; -.
DR Pharos; O00418; Tchem.
DR PRO; PR:O00418; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O00418; protein.
DR Bgee; ENSG00000103319; Expressed in skin of leg and 102 other tissues.
DR ExpressionAtlas; O00418; baseline and differential.
DR Genevisible; O00418; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0004686; F:elongation factor-2 kinase activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0008135; F:translation factor activity, RNA binding; TAS:ProtInc.
DR GO; GO:0071454; P:cellular response to anoxia; IEA:Ensembl.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEA:Ensembl.
DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IEA:Ensembl.
DR GO; GO:0045807; P:positive regulation of endocytosis; IEA:Ensembl.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0031952; P:regulation of protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1990637; P:response to prolactin; IEA:Ensembl.
DR GO; GO:0006414; P:translational elongation; TAS:ProtInc.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR017400; eEF-2K.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR004166; MHCK_EF2_kinase.
DR InterPro; IPR006597; Sel1-like.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF02816; Alpha_kinase; 1.
DR Pfam; PF08238; Sel1; 3.
DR PIRSF; PIRSF038139; Elongation_factor_2_kinase; 1.
DR SMART; SM00811; Alpha_kinase; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51158; ALPHA_KINASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Calcium; Calmodulin-binding;
KW Kinase; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..725
FT /note="Eukaryotic elongation factor 2 kinase"
FT /id="PRO_0000086936"
FT DOMAIN 116..326
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..94
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000269|PubMed:11015200"
FT REGION 352..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..477
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 379..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..474
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 296..302
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 61
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903"
FT MOD_RES 66
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08796"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 78
FT /note="Phosphoserine; by autocatalysis and TRPM7"
FT /evidence="ECO:0000269|PubMed:21112387,
FT ECO:0000269|PubMed:22216903, ECO:0007744|PubMed:23186163"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 348
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 353
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 359
FT /note="Phosphoserine; by MAPK13 and CDK1"
FT /evidence="ECO:0000269|PubMed:11500363,
FT ECO:0000269|PubMed:18337751"
FT MOD_RES 366
FT /note="Phosphoserine; by autocatalysis, RPS6KA1 and
FT RPS6KB1"
FT /evidence="ECO:0000269|PubMed:11500364,
FT ECO:0000269|PubMed:22216903"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08796"
FT MOD_RES 398
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:14709557"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 445
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 474
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 491
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:22216903,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 500
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P70531"
FT VARIANT 23
FT /note="H -> R (in dbSNP:rs9935059)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_033915"
FT VARIANT 75
FT /note="P -> A (in dbSNP:rs17841292)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_033916"
FT VARIANT 291
FT /note="T -> M (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs147978363)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041534"
FT VARIANT 361
FT /note="Q -> R (in dbSNP:rs4783453)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9144159"
FT /id="VAR_058405"
FT VARIANT 433
FT /note="R -> W (in dbSNP:rs56137739)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041535"
FT VARIANT 609
FT /note="D -> H"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041536"
FT MUTAGEN 78
FT /note="S->A: Decreased kinase activity."
FT /evidence="ECO:0000269|PubMed:22216903"
FT MUTAGEN 348
FT /note="T->A: Decreased kinase activity."
FT /evidence="ECO:0000269|PubMed:22216903"
FT MUTAGEN 366
FT /note="S->A: Abrogates phosphorylation by RPS6KB1."
FT /evidence="ECO:0000269|PubMed:11500364,
FT ECO:0000269|PubMed:22216903"
FT MUTAGEN 366
FT /note="S->A: Decreased kinase activity."
FT /evidence="ECO:0000269|PubMed:11500364,
FT ECO:0000269|PubMed:22216903"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:5J8H"
FT HELIX 81..91
FT /evidence="ECO:0007829|PDB:5J8H"
FT STRAND 562..564
FT /evidence="ECO:0007829|PDB:6NX4"
FT HELIX 591..595
FT /evidence="ECO:0007829|PDB:6NX4"
FT HELIX 598..607
FT /evidence="ECO:0007829|PDB:6NX4"
FT HELIX 610..622
FT /evidence="ECO:0007829|PDB:6NX4"
FT TURN 624..626
FT /evidence="ECO:0007829|PDB:6NX4"
FT HELIX 633..640
FT /evidence="ECO:0007829|PDB:5KS5"
FT STRAND 649..653
FT /evidence="ECO:0007829|PDB:6NX4"
FT HELIX 664..676
FT /evidence="ECO:0007829|PDB:5KS5"
FT STRAND 680..682
FT /evidence="ECO:0007829|PDB:6NX4"
FT HELIX 686..702
FT /evidence="ECO:0007829|PDB:5KS5"
FT HELIX 706..721
FT /evidence="ECO:0007829|PDB:5KS5"
SQ SEQUENCE 725 AA; 82144 MW; 9D2900E50EFF12DA CRC64;
MADEDLIFRL EGVDGGQSPR AGHDGDSDGD SDDEEGYFIC PITDDPSSNQ NVNSKVNKYY
SNLTKSERYS SSGSPANSFH FKEAWKHAIQ KAKHMPDPWA EFHLEDIATE RATRHRYNAV
TGEWLDDEVL IKMASQPFGR GAMRECFRTK KLSNFLHAQQ WKGASNYVAK RYIEPVDRDV
YFEDVRLQME AKLWGEEYNR HKPPKQVDIM QMCIIELKDR PGKPLFHLEH YIEGKYIKYN
SNSGFVRDDN IRLTPQAFSH FTFERSGHQL IVVDIQGVGD LYTDPQIHTE TGTDFGDGNL
GVRGMALFFY SHACNRICES MGLAPFDLSP RERDAVNQNT KLLQSAKTIL RGTEEKCGSP
QVRTLSGSRP PLLRPLSENS GDENMSDVTF DSLPSSPSSA TPHSQKLDHL HWPVFSDLDN
MASRDHDHLD NHRESENSGD SGYPSEKRGE LDDPEPREHG HSYSNRKYES DEDSLGSSGR
VCVEKWNLLN SSRLHLPRAS AVALEVQRLN ALDLEKKIGK SILGKVHLAM VRYHEGGRFC
EKGEEWDQES AVFHLEHAAN LGELEAIVGL GLMYSQLPHH ILADVSLKET EENKTKGFDY
LLKAAEAGDR QSMILVARAF DSGQNLSPDR CQDWLEALHW YNTALEMTDC DEGGEYDGMQ
DEPRYMMLAR EAEMLFTGGY GLEKDPQRSG DLYTQAAEAA MEAMKGRLAN QYYQKAEEAW
AQMEE
