EF2_HUMAN
ID EF2_HUMAN Reviewed; 858 AA.
AC P13639; B2RMP5; D6W618; Q58J86;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Elongation factor 2;
DE Short=EF-2;
GN Name=EEF2; Synonyms=EF2;
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].
RC TISSUE=Ovary;
RX PubMed=2610926; DOI=10.1515/bchm3.1989.370.2.1071;
RA Rapp G., Klaudiny J., Hagendorff G., Luck M.R., Heinz K.;
RT "Complete sequence of the coding region of human elongation factor 2 (EF-2)
RT by enzymatic amplification of cDNA from human ovarian granulosa cells.";
RL Biol. Chem. Hoppe-Seyler 370:1071-1075(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1596361; DOI=10.1515/bchm3.1992.373.1.201;
RA Hanes J., Freudenstein J., Rapp G., Scheit K.H.;
RT "Construction of a plasmid containing the complete coding region of human
RT elongation factor 2.";
RL Biol. Chem. Hoppe-Seyler 373:201-204(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Peripheral blood;
RA Ustek D., Bektas M., Cakiris A., Oku B., Bermek E.;
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 501-858.
RX PubMed=2840927; DOI=10.1515/bchm3.1988.369.1.247;
RA Rapp G., Mucha J., Einspanier R., Luck M., Scheit K.H.;
RT "Cloning and sequence analysis of a cDNA from human ovarian granulosa cells
RT encoding the C-terminal part of human elongation factor 2.";
RL Biol. Chem. Hoppe-Seyler 369:247-250(1988).
RN [7]
RP PROTEIN SEQUENCE OF 796-801, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP CLEAVAGE OF INITIATOR METHIONINE.
RA Bienvenut W.V.;
RL Submitted (AUG-2001) to UniProtKB.
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [10]
RP ISGYLATION.
RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132;
RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J.,
RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.;
RT "Proteomic identification of proteins conjugated to ISG15 in mouse and
RT human cells.";
RL Biochem. Biophys. Res. Commun. 336:496-506(2005).
RN [11]
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 [12]
RP MUTAGENESIS OF HIS-715, AND DIPHTHAMIDE AT HIS-715.
RX PubMed=16901746; DOI=10.1016/j.mrgentox.2006.06.027;
RA Ivankovic M., Rubelj I., Matulic M., Reich E., Brdar B.;
RT "Site-specific mutagenesis of the histidine precursor of diphthamide in the
RT human elongation factor-2 gene confers resistance to diphtheria toxin.";
RL Mutat. Res. 609:34-42(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-435 AND SER-502, AND
RP 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 [14]
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 [15]
RP IDENTIFICATION IN THE SURF COMPLEX.
RX PubMed=19417104; DOI=10.1101/gad.1767209;
RA Yamashita A., Izumi N., Kashima I., Ohnishi T., Saari B., Katsuhata Y.,
RA Muramatsu R., Morita T., Iwamatsu A., Hachiya T., Kurata R., Hirano H.,
RA Anderson P., Ohno S.;
RT "SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate
RT remodeling of the mRNA surveillance complex during nonsense-mediated mRNA
RT decay.";
RL Genes Dev. 23:1091-1105(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-235; LYS-239; LYS-272; LYS-275
RP AND LYS-445, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57; THR-59 AND THR-435, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; THR-57 AND THR-59, 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 [20]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [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 IDENTIFICATION BY MASS 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-57; THR-59; THR-435; SER-502
RP AND SER-595, 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 [23]
RP PHOSPHORYLATION AT THR-57 AND SER-595, AND MUTAGENESIS OF SER-595 AND
RP HIS-599.
RX PubMed=23184662; DOI=10.1128/mcb.01270-12;
RA Hizli A.A., Chi Y., Swanger J., Carter J.H., Liao Y., Welcker M.,
RA Ryazanov A.G., Clurman B.E.;
RT "Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-
RT cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase.";
RL Mol. Cell. Biol. 33:596-604(2013).
RN [24]
RP PHOSPHORYLATION AT TYR-265 AND TYR-373 BY CSK, SUMOYLATION AT LYS-322 AND
RP LYS-529, PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=24648518; DOI=10.1074/jbc.m113.546481;
RA Yao Q., Liu B.Q., Li H., McGarrigle D., Xing B.W., Zhou M.T., Wang Z.,
RA Zhang J.J., Huang X.Y., Guo L.;
RT "C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic
RT elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear
RT translocation of eEF2.";
RL J. Biol. Chem. 289:12666-12678(2014).
RN [25]
RP METHYLATION AT LYS-525.
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).
RN [26]
RP 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 [27]
RP INTERACTION WITH RBPMS2, AND SUBCELLULAR LOCATION.
RX PubMed=25064856; DOI=10.1093/nar/gku692;
RA Sagnol S., Yang Y., Bessin Y., Allemand F., Hapkova I., Notarnicola C.,
RA Guichou J.F., Faure S., Labesse G., de Santa Barbara P.;
RT "Homodimerization of RBPMS2 through a new RRM-interaction motif is
RT necessary to control smooth muscle plasticity.";
RL Nucleic Acids Res. 42:10173-10184(2014).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-239, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [29]
RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [30]
RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS) IN COMPLEX WITH 80S
RP RIBOSOME.
RX PubMed=23636399; DOI=10.1038/nature12104;
RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M.,
RA Wilson D.N., Beckmann R.;
RT "Structures of the human and Drosophila 80S ribosome.";
RL Nature 497:80-85(2013).
RN [31]
RP VARIANT SCA26 HIS-596, AND CHARACTERIZATION OF VARIANT SCA26 HIS-596.
RX PubMed=23001565; DOI=10.1093/hmg/dds392;
RA Hekman K.E., Yu G.Y., Brown C.D., Zhu H., Du X., Gervin K., Undlien D.E.,
RA Peterson A., Stevanin G., Clark H.B., Pulst S.M., Bird T.D., White K.P.,
RA Gomez C.M.;
RT "A conserved eEF2 coding variant in SCA26 leads to loss of translational
RT fidelity and increased susceptibility to proteostatic insult.";
RL Hum. Mol. Genet. 21:5472-5483(2012).
CC -!- FUNCTION: Catalyzes the GTP-dependent ribosomal translocation step
CC during translation elongation. During this step, the ribosome changes
CC from the pre-translocational (PRE) to the post-translocational (POST)
CC state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound
CC deacylated tRNA move to the P and E sites, respectively. Catalyzes the
CC coordinated movement of the two tRNA molecules, the mRNA and
CC conformational changes in the ribosome.
CC -!- SUBUNIT: Component of the mRNA surveillance SURF complex, at least
CC composed of ERF1, ERF3 (ERF3A or ERF3B), EEF2, UPF1/RENT1, SMG1, SMG8
CC and SMG9 (PubMed:19417104). Interacts with RBPMS2 (PubMed:25064856).
CC {ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:25064856}.
CC -!- INTERACTION:
CC P13639; Q99714: HSD17B10; NbExp=3; IntAct=EBI-352560, EBI-79964;
CC P13639; P42858: HTT; NbExp=3; IntAct=EBI-352560, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25064856}. Nucleus
CC {ECO:0000269|PubMed:24648518}. Note=Phosphorylation by CSK promotes
CC cleavage and SUMOylation-dependent nuclear translocation of the C-
CC terminal cleavage product. {ECO:0000269|PubMed:24648518}.
CC -!- PTM: Phosphorylation by EF-2 kinase completely inactivates EF-2; it
CC requires prior phosphorylation by CDK2 at Ser-595 during mitotic
CC prometaphase. Phosphorylation by CSK promotes SUMOylation, proteolytic
CC cleavage, and nuclear translocation if the C-terminal fragment.
CC {ECO:0000269|PubMed:23184662, ECO:0000269|PubMed:24648518}.
CC -!- PTM: Diphthamide is 2-[3-carboxyamido-3-(trimethyl-
CC ammonio)propyl]histidine (By similarity).
CC {ECO:0000250|UniProtKB:P05197}.
CC -!- PTM: (Microbial infection) Diphthamide can be ADP-ribosylated by
CC diphtheria toxin and by Pseudomonas exotoxin A, thus arresting protein
CC synthesis. {ECO:0000269|PubMed:16901746}.
CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}.
CC -!- PTM: Proteolytically processed at two sites following phosphorylation
CC by CSK. {ECO:0000269|PubMed:24648518}.
CC -!- PTM: SUMOylated following phosphorylation by CSK, promotes proteolytic
CC cleavage. {ECO:0000269|PubMed:24648518}.
CC -!- DISEASE: Spinocerebellar ataxia 26 (SCA26) [MIM:609306]: A form of
CC spinocerebellar ataxia, a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. {ECO:0000269|PubMed:23001565}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the TRAFAC class translation factor GTPase
CC superfamily. Classic translation factor GTPase family. EF-G/EF-2
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU01059}.
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DR EMBL; X51466; CAA35829.1; -; mRNA.
DR EMBL; Z11692; CAA77750.1; -; mRNA.
DR EMBL; AY942181; AAX34409.1; -; mRNA.
DR EMBL; CH471139; EAW69274.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69275.1; -; Genomic_DNA.
DR EMBL; BC126259; AAI26260.1; -; mRNA.
DR EMBL; BC136313; AAI36314.1; -; mRNA.
DR EMBL; M19997; AAA50388.1; -; mRNA.
DR CCDS; CCDS12117.1; -.
DR PIR; S18294; EFHU2.
DR RefSeq; NP_001952.1; NM_001961.3.
DR PDB; 4V6X; EM; 5.00 A; Az=1-858.
DR PDB; 6D9J; EM; 3.20 A; 9=3-858.
DR PDB; 6Z6M; EM; 3.10 A; CB=1-858.
DR PDB; 6Z6N; EM; 2.90 A; CB=1-858.
DR PDBsum; 4V6X; -.
DR PDBsum; 6D9J; -.
DR PDBsum; 6Z6M; -.
DR PDBsum; 6Z6N; -.
DR AlphaFoldDB; P13639; -.
DR SMR; P13639; -.
DR BioGRID; 108258; 378.
DR CORUM; P13639; -.
DR IntAct; P13639; 126.
DR MINT; P13639; -.
DR STRING; 9606.ENSP00000307940; -.
DR ChEMBL; CHEMBL1795108; -.
DR DrugBank; DB02059; Adenosine-5-Diphosphoribose.
DR DrugBank; DB03223; Diphthamide.
DR DrugBank; DB11823; Esketamine.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR DrugBank; DB12688; Moxetumomab pasudotox.
DR DrugBank; DB08348; N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDE.
DR MoonProt; P13639; -.
DR GlyGen; P13639; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P13639; -.
DR MetOSite; P13639; -.
DR PhosphoSitePlus; P13639; -.
DR SwissPalm; P13639; -.
DR BioMuta; EEF2; -.
DR DMDM; 119172; -.
DR REPRODUCTION-2DPAGE; IPI00186290; -.
DR EPD; P13639; -.
DR jPOST; P13639; -.
DR MassIVE; P13639; -.
DR MaxQB; P13639; -.
DR PaxDb; P13639; -.
DR PeptideAtlas; P13639; -.
DR PRIDE; P13639; -.
DR ProteomicsDB; 52947; -.
DR Antibodypedia; 23430; 572 antibodies from 38 providers.
DR DNASU; 1938; -.
DR Ensembl; ENST00000309311.7; ENSP00000307940.5; ENSG00000167658.16.
DR GeneID; 1938; -.
DR KEGG; hsa:1938; -.
DR MANE-Select; ENST00000309311.7; ENSP00000307940.5; NM_001961.4; NP_001952.1.
DR UCSC; uc002lze.4; human.
DR CTD; 1938; -.
DR DisGeNET; 1938; -.
DR GeneCards; EEF2; -.
DR HGNC; HGNC:3214; EEF2.
DR HPA; ENSG00000167658; Low tissue specificity.
DR MalaCards; EEF2; -.
DR MIM; 130610; gene.
DR MIM; 609306; phenotype.
DR neXtProt; NX_P13639; -.
DR OpenTargets; ENSG00000167658; -.
DR Orphanet; 101112; Spinocerebellar ataxia type 26.
DR PharmGKB; PA27650; -.
DR VEuPathDB; HostDB:ENSG00000167658; -.
DR eggNOG; KOG0469; Eukaryota.
DR GeneTree; ENSGT00940000154662; -.
DR HOGENOM; CLU_002794_11_1_1; -.
DR InParanoid; P13639; -.
DR OMA; MGGAEIN; -.
DR OrthoDB; 140796at2759; -.
DR PhylomeDB; P13639; -.
DR TreeFam; TF300575; -.
DR BRENDA; 3.6.5.3; 2681.
DR PathwayCommons; P13639; -.
DR Reactome; R-HSA-156902; Peptide chain elongation.
DR Reactome; R-HSA-5336415; Uptake and function of diphtheria toxin.
DR Reactome; R-HSA-5358493; Synthesis of diphthamide-EEF2.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8876725; Protein methylation.
DR SignaLink; P13639; -.
DR SIGNOR; P13639; -.
DR BioGRID-ORCS; 1938; 830 hits in 1065 CRISPR screens.
DR ChiTaRS; EEF2; human.
DR GeneWiki; EEF2; -.
DR GenomeRNAi; 1938; -.
DR Pharos; P13639; Tchem.
DR PRO; PR:P13639; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P13639; protein.
DR Bgee; ENSG00000167658; Expressed in parotid gland and 209 other tissues.
DR ExpressionAtlas; P13639; baseline and differential.
DR Genevisible; P13639; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005844; C:polysome; IEA:Ensembl.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IDA:FlyBase.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0003746; F:translation elongation factor activity; IBA:GO_Central.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0006414; P:translational elongation; IBA:GO_Central.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR041095; EFG_II.
DR InterPro; IPR035647; EFG_III/V.
DR InterPro; IPR000640; EFG_V-like.
DR InterPro; IPR004161; EFTu-like_2.
DR InterPro; IPR031157; G_TR_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR000795; T_Tr_GTP-bd_dom.
DR InterPro; IPR009000; Transl_B-barrel_sf.
DR InterPro; IPR005517; Transl_elong_EFG/EF2_IV.
DR Pfam; PF00679; EFG_C; 1.
DR Pfam; PF14492; EFG_III; 1.
DR Pfam; PF03764; EFG_IV; 1.
DR Pfam; PF00009; GTP_EFTU; 1.
DR Pfam; PF03144; GTP_EFTU_D2; 1.
DR PRINTS; PR00315; ELONGATNFCT.
DR SMART; SM00838; EFG_C; 1.
DR SMART; SM00889; EFG_IV; 1.
DR SUPFAM; SSF50447; SSF50447; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF54980; SSF54980; 2.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS00301; G_TR_1; 1.
DR PROSITE; PS51722; G_TR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Cytoplasm;
KW Direct protein sequencing; Disease variant; Elongation factor; GTP-binding;
KW Isopeptide bond; Methylation; Neurodegeneration; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Protein biosynthesis; Reference proteome;
KW Spinocerebellar ataxia; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:25944712"
FT CHAIN 2..858
FT /note="Elongation factor 2"
FT /id="PRO_0000091000"
FT DOMAIN 17..362
FT /note="tr-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT BINDING 26..33
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 104..108
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 158..161
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT SITE 586..587
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:24648518"
FT SITE 605..606
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:24648518"
FT MOD_RES 54
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 57
FT /note="Phosphothreonine; by EEF2K"
FT /evidence="ECO:0000269|PubMed:23184662,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 59
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 152
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P58252"
FT MOD_RES 235
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 239
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 265
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000269|PubMed:24648518"
FT MOD_RES 272
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 272
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P58252"
FT MOD_RES 275
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05197"
FT MOD_RES 373
FT /note="Phosphotyrosine; by CSK"
FT /evidence="ECO:0000269|PubMed:24648518"
FT MOD_RES 435
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 439
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P58252"
FT MOD_RES 445
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 525
FT /note="N6,N6,N6-trimethyllysine; by EEF2KMT"
FT /evidence="ECO:0000269|PubMed:25231979"
FT MOD_RES 572
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P58252"
FT MOD_RES 595
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000269|PubMed:23184662,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 619
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P58252"
FT MOD_RES 715
FT /note="(Microbial infection) ADP-ribosyldiphthamide"
FT /evidence="ECO:0000269|PubMed:16901746"
FT MOD_RES 715
FT /note="Diphthamide"
FT /evidence="ECO:0000269|PubMed:16901746"
FT CROSSLNK 239
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:24648518"
FT CROSSLNK 529
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:24648518"
FT VARIANT 596
FT /note="P -> H (in SCA26; compromises the mechanics of
FT translocation; dbSNP:rs587777052)"
FT /evidence="ECO:0000269|PubMed:23001565"
FT /id="VAR_070792"
FT MUTAGEN 595
FT /note="S->A: Strongly reduced phosphorylation at Thr-57."
FT /evidence="ECO:0000269|PubMed:23184662"
FT MUTAGEN 599
FT /note="H->P: Strongly reduced phosphorylation at Thr-57."
FT /evidence="ECO:0000269|PubMed:23184662"
FT MUTAGEN 715
FT /note="H->L,M,N,Q: Confers resistance to diphtheria toxin."
FT /evidence="ECO:0000269|PubMed:16901746"
SQ SEQUENCE 858 AA; 95338 MW; 78BD1710236C0D9C CRC64;
MVNFTVDQIR AIMDKKANIR NMSVIAHVDH GKSTLTDSLV CKAGIIASAR AGETRFTDTR
KDEQERCITI KSTAISLFYE LSENDLNFIK QSKDGAGFLI NLIDSPGHVD FSSEVTAALR
VTDGALVVVD CVSGVCVQTE TVLRQAIAER IKPVLMMNKM DRALLELQLE PEELYQTFQR
IVENVNVIIS TYGEGESGPM GNIMIDPVLG TVGFGSGLHG WAFTLKQFAE MYVAKFAAKG
EGQLGPAERA KKVEDMMKKL WGDRYFDPAN GKFSKSATSP EGKKLPRTFC QLILDPIFKV
FDAIMNFKKE ETAKLIEKLD IKLDSEDKDK EGKPLLKAVM RRWLPAGDAL LQMITIHLPS
PVTAQKYRCE LLYEGPPDDE AAMGIKSCDP KGPLMMYISK MVPTSDKGRF YAFGRVFSGL
VSTGLKVRIM GPNYTPGKKE DLYLKPIQRT ILMMGRYVEP IEDVPCGNIV GLVGVDQFLV
KTGTITTFEH AHNMRVMKFS VSPVVRVAVE AKNPADLPKL VEGLKRLAKS DPMVQCIIEE
SGEHIIAGAG ELHLEICLKD LEEDHACIPI KKSDPVVSYR ETVSEESNVL CLSKSPNKHN
RLYMKARPFP DGLAEDIDKG EVSARQELKQ RARYLAEKYE WDVAEARKIW CFGPDGTGPN
ILTDITKGVQ YLNEIKDSVV AGFQWATKEG ALCEENMRGV RFDVHDVTLH ADAIHRGGGQ
IIPTARRCLY ASVLTAQPRL MEPIYLVEIQ CPEQVVGGIY GVLNRKRGHV FEESQVAGTP
MFVVKAYLPV NESFGFTADL RSNTGGQAFP QCVFDHWQIL PGDPFDNSSR PSQVVAETRK
RKGLKEGIPA LDNFLDKL
