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 28-JAN-2026, entry version 216. 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. CC {ECO:0000250|UniProtKB:P70531}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_037434.2; NM_013302.5. 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 PDB; 8FNY; X-ray; 2.22 A; A/C=70-358, A/C=490-725. DR PDB; 8FO6; X-ray; 2.55 A; A=70-358, A=490-725. DR PDB; 8GM4; X-ray; 2.12 A; A=70-358, A=490-725. DR PDB; 8GM5; X-ray; 2.12 A; A=70-358, A=490-725. DR PDBsum; 5J8H; -. DR PDBsum; 5KS5; -. DR PDBsum; 6NX4; -. DR PDBsum; 7SHQ; -. DR PDBsum; 8FNY; -. DR PDBsum; 8FO6; -. DR PDBsum; 8GM4; -. DR PDBsum; 8GM5; -. DR AlphaFoldDB; O00418; -. DR SMR; O00418; -. DR BioGRID; 118953; 62. DR BioGRID; 3193665; 1. DR ELM; O00418; -. DR FunCoup; O00418; 1312. DR IntAct; O00418; 27. DR MINT; O00418; -. DR STRING; 9606.ENSP00000263026; -. DR BindingDB; O00418; -. DR ChEMBL; CHEMBL5026; -. DR DrugBank; DB01259; Lapatinib. 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 jPOST; O00418; -. DR MassIVE; O00418; -. DR PaxDb; 9606-ENSP00000263026; -. DR PeptideAtlas; O00418; -. DR ProteomicsDB; 47876; -. DR Pumba; O00418; -. DR Antibodypedia; 25835; 476 antibodies from 35 providers. DR DNASU; 29904; -. DR Ensembl; ENST00000263026.10; ENSP00000263026.5; ENSG00000103319.13. 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 AGR; HGNC:24615; -. DR ClinPGx; PA134992891; -. 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 OpenTargets; ENSG00000103319; -. DR VEuPathDB; HostDB:ENSG00000103319; -. DR eggNOG; ENOG502QVA3; Eukaryota. DR GeneTree; ENSGT00940000157839; -. DR HOGENOM; CLU_382143_0_0_1; -. DR InParanoid; O00418; -. DR OMA; CLQMEAK; -. DR OrthoDB; 301415at2759; -. DR PAN-GO; O00418; 1 GO annotation based on evolutionary models. DR PhylomeDB; O00418; -. 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 Agora; ENSG00000103319; -. DR BioGRID-ORCS; 29904; 10 hits in 1191 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 103 other cell types or tissues. DR ExpressionAtlas; O00418; baseline and differential. 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:0098978; C:glutamatergic synapse; 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: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:0031037; P:myosin II filament disassembly; IBA:GO_Central. 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:0140245; P:regulation of translation at postsynapse; 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 CDD; cd16967; Alpha_kinase_eEF2K; 1. DR DisProt; DP04157; -. DR FunFam; 1.25.40.10:FF:000229; Eukaryotic elongation factor 2 kinase; 1. DR FunFam; 3.20.200.10:FF:000002; Eukaryotic elongation factor 2 kinase; 1. DR FunFam; 3.30.200.20:FF:000230; Eukaryotic elongation factor 2 kinase; 1. DR FunFam; 3.30.200.20:FF:000336; Eukaryotic elongation factor 2 kinase; 1. DR Gene3D; 3.20.200.10; MHCK/EF2 kinase; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 2. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR InterPro; IPR004166; a-kinase_dom. DR InterPro; IPR051852; Alpha-type_PK. DR InterPro; IPR017400; eEF-2K. DR InterPro; IPR047588; eEF2K_a_kinase_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR PANTHER; PTHR45992:SF2; EUKARYOTIC ELONGATION FACTOR 2 KINASE; 1. DR PANTHER; PTHR45992; EUKARYOTIC ELONGATION FACTOR 2 KINASE-RELATED; 1. DR Pfam; PF02816; Alpha_kinase; 1. DR PIRSF; PIRSF038139; Elongation_factor_2_kinase; 1. DR SMART; SM00811; Alpha_kinase; 1. DR SUPFAM; SSF81901; HCP-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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; Proteomics identification; KW Reference proteome; 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..38 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 1..12 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 27..36 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 363..377 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 386..404 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 423..436 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 445..469 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 82..94 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 110..118 FT /evidence="ECO:0007829|PDB:8GM4" FT TURN 119..122 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 123..133 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 142..151 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 154..158 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 161..163 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 165..174 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 178..199 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 218..220 FT /evidence="ECO:0007829|PDB:7SHQ" FT STRAND 225..230 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 236..238 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 248..250 FT /evidence="ECO:0007829|PDB:7SHQ" FT HELIX 253..265 FT /evidence="ECO:0007829|PDB:8GM4" FT TURN 266..268 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 269..273 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 276..278 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 286..291 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 296..298 FT /evidence="ECO:0007829|PDB:8FO6" FT HELIX 302..311 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 316..320 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 330..337 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 340..344 FT /evidence="ECO:0007829|PDB:8FNY" FT HELIX 502..508 FT /evidence="ECO:0007829|PDB:8GM5" FT HELIX 517..536 FT /evidence="ECO:0007829|PDB:8GM4" FT TURN 537..539 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 548..560 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 564..574 FT /evidence="ECO:0007829|PDB:8GM4" FT TURN 581..584 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 591..606 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 610..622 FT /evidence="ECO:0007829|PDB:8GM4" FT TURN 624..626 FT /evidence="ECO:0007829|PDB:6NX4" FT HELIX 634..645 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 649..653 FT /evidence="ECO:0007829|PDB:6NX4" FT HELIX 664..677 FT /evidence="ECO:0007829|PDB:8GM4" FT STRAND 680..682 FT /evidence="ECO:0007829|PDB:6NX4" FT HELIX 686..702 FT /evidence="ECO:0007829|PDB:8GM4" FT HELIX 706..720 FT /evidence="ECO:0007829|PDB:8GM4" 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 //