EF2K_RAT
ID EF2K_RAT Reviewed; 724 AA.
AC P70531; O09089;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 158.
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:9144159};
DE AltName: Full=Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase;
GN Name=Eef2k {ECO:0000312|RGD:2538};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RC TISSUE=Skeletal muscle;
RX PubMed=8663182; DOI=10.1074/jbc.271.29.17547;
RA Redpath N.T., Price N.T., Proud C.G.;
RT "Cloning and expression of cDNA encoding protein synthesis elongation
RT factor-2 kinase.";
RL J. Biol. Chem. 271:17547-17554(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New England Deaconess Hospital; TISSUE=Pheochromocytoma;
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 [3]
RP AUTOPHOSPHORYLATION.
RX PubMed=8514778; DOI=10.1016/s0021-9258(19)38667-3;
RA Mitsui K., Brady M., Palfrey H.C., Nairn A.C.;
RT "Purification and characterization of calmodulin-dependent protein kinase
RT III from rabbit reticulocytes and rat pancreas.";
RL J. Biol. Chem. 268:13422-13433(1993).
RN [4]
RP PHOSPHORYLATION AT SER-499 BY PKA.
RX PubMed=11171059; DOI=10.1042/0264-6021:3530621;
RA Diggle T.A., Subkhankulova T., Lilley K.S., Shikotra N., Willis A.E.,
RA Redpath N.T.;
RT "Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-
RT dependent protein kinase induces Ca2+/calmodulin-independent activity.";
RL Biochem. J. 353:621-626(2001).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-73; THR-347; SER-365;
RP SER-444; SER-469; SER-473 AND SER-476, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By similarity). {ECO:0000250}.
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:9144159};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21437;
CC Evidence={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:0000269|PubMed:9144159}.
CC -!- SUBUNIT: Monomer or homodimer (Probable). Interacts with
CC Calmodulin/CALM1; this interaction is strictly required for
CC phosphorylation activity (By similarity).
CC {ECO:0000250|UniProtKB:O00418, ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with high levels in reticulocytes
CC and skeletal muscle. {ECO:0000269|PubMed:8663182}.
CC -!- DOMAIN: The catalytic domain is located to N-terminal region. The
CC neighbor region contains the calmodulin-binding domain (By similarity).
CC {ECO:0000250}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Autophosphorylated at multiple residues, Thr-347 being the major
CC site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-397
CC leading to EEF2K activation and protein synthesis inhibition.
CC Phosphorylated by TRPM7 at Ser-77 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-358 or RPS6KA1 and RPS6KB1 at Ser-365 instead decrease
CC EEF2K activity and promote protein synthesis (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Alpha-type
CC protein kinase family. {ECO:0000305}.
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DR EMBL; X96426; CAA65286.1; -; mRNA.
DR EMBL; U93849; AAB58272.1; -; mRNA.
DR RefSeq; NP_037079.1; NM_012947.2.
DR RefSeq; XP_006230218.1; XM_006230156.3.
DR RefSeq; XP_006230219.1; XM_006230157.3.
DR RefSeq; XP_006230220.1; XM_006230158.3.
DR AlphaFoldDB; P70531; -.
DR SMR; P70531; -.
DR ELM; P70531; -.
DR STRING; 10116.ENSRNOP00000022726; -.
DR BindingDB; P70531; -.
DR ChEMBL; CHEMBL3325307; -.
DR iPTMnet; P70531; -.
DR PhosphoSitePlus; P70531; -.
DR PaxDb; P70531; -.
DR PRIDE; P70531; -.
DR Ensembl; ENSRNOT00000022726; ENSRNOP00000022726; ENSRNOG00000016448.
DR GeneID; 25435; -.
DR KEGG; rno:25435; -.
DR UCSC; RGD:2538; rat.
DR CTD; 29904; -.
DR RGD; 2538; Eef2k.
DR eggNOG; ENOG502QVA3; Eukaryota.
DR GeneTree; ENSGT00940000157839; -.
DR HOGENOM; CLU_382143_0_0_1; -.
DR InParanoid; P70531; -.
DR OMA; LEAIITM; -.
DR OrthoDB; 741011at2759; -.
DR PhylomeDB; P70531; -.
DR TreeFam; TF316085; -.
DR BRENDA; 2.7.11.20; 5301.
DR Reactome; R-RNO-166208; mTORC1-mediated signalling.
DR PRO; PR:P70531; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016448; Expressed in skeletal muscle tissue and 20 other tissues.
DR Genevisible; P70531; RN.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO-UCL.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
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; ISS:UniProtKB.
DR GO; GO:0004686; F:elongation factor-2 kinase activity; IMP:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0071454; P:cellular response to anoxia; IEP:RGD.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEP:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IMP:RGD.
DR GO; GO:0045807; P:positive regulation of endocytosis; IMP:RGD.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0031952; P:regulation of protein autophosphorylation; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; IEP:RGD.
DR GO; GO:1990637; P:response to prolactin; IEP:RGD.
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; 4.
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 Acetylation; ATP-binding; Calcium; Calmodulin-binding; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT CHAIN 2..724
FT /note="Eukaryotic elongation factor 2 kinase"
FT /id="PRO_0000086938"
FT DOMAIN 115..325
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
FT REGION 11..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..93
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT REGION 353..476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..473
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 295..301
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08796"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 77
FT /note="Phosphoserine; by autocatalysis and TRPM7"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 347
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 352
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 358
FT /note="Phosphoserine; by MAPK13 and CDK1"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08796"
FT MOD_RES 397
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 499
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:11171059"
SQ SEQUENCE 724 AA; 81489 MW; E4DDD832AE9F7165 CRC64;
MADEDLIFRL EGVDGGGSSG AGRHGDSDTD SDDDEGYFIC PITDDHMSNQ NVNSKGQGYY
NNLLKTECGS TGSPASSFHF KEAWKHAIEK AKHMPDPWAE FHLEDIATEH ATRHRYNAVT
GEWLKDEVLI KMASQPFGRG AMRECFRTKK LSNFLHAQHW KGASNYVAKR YLEPVDRSVY
FEDVQLQMEA KLWGEEYNRH KPPKQVDIMQ MCIIELKDRQ GQPLFHLEHY IEGKYIKYNS
NSGFVRDDNI RLTPQAFSHF TFERSGHQLI VVDIQGVGDL YTDPQIHTEK GTDFGDGNLG
VRGMALFFYS HACNRICQSM GLAPFDLSPR EQDAVNQSTK LLQSAKTILR GTEEKCGSPR
IRTLSGSRPP LLLRLSENSG DENMSDVTFD SLPSSPSSAT PHSQKLDHLH WPVFGDLDNM
GPRDHDRMDN HRDSENSGDS GYPSEKRSDL DDPEPREHGH SNGNRRPESD EDSLGSSGRV
CVETWNLLNP SRLHLPRPSA VALEVQRLNA LDLGRKIGKS VLGKVHLAMV RYHEGGRFCE
KDEEWDQESA IFHLEHAADL GELEAIVGLG LMYSQLPHHI LADVSLEETE ENKTKGFDYL
LKAAEAGDRQ SMILVARAFD TGLNLSPDRC QDWSEALHWY NTALETTDCD EGGEYDGIQD
EPQYALLARE AEMLLTGGFG LDKNPQRSGD LYTQAAEAAM EAMKGRLANQ YYEKAEEAWA
QMEE
