EF2K_MOUSE
ID EF2K_MOUSE Reviewed; 724 AA.
AC O08796;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 172.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND FUNCTION.
RC STRAIN=BALB/cJ; TISSUE=Spleen;
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 MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-391 AND SER-444, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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: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: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 -!- 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: Ubiquitously expressed. Particularly abundant in
CC skeletal muscle and heart.
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: 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; U93848; AAB58271.1; -; mRNA.
DR EMBL; BC003433; AAH03433.1; -; mRNA.
DR CCDS; CCDS21796.1; -.
DR RefSeq; NP_001254639.1; NM_001267710.1.
DR RefSeq; NP_001254640.1; NM_001267711.1.
DR RefSeq; NP_031934.1; NM_007908.4.
DR RefSeq; XP_006507405.1; XM_006507342.3.
DR RefSeq; XP_006507406.1; XM_006507343.3.
DR AlphaFoldDB; O08796; -.
DR SMR; O08796; -.
DR IntAct; O08796; 1.
DR STRING; 10090.ENSMUSP00000046595; -.
DR iPTMnet; O08796; -.
DR PhosphoSitePlus; O08796; -.
DR EPD; O08796; -.
DR jPOST; O08796; -.
DR MaxQB; O08796; -.
DR PaxDb; O08796; -.
DR PeptideAtlas; O08796; -.
DR PRIDE; O08796; -.
DR ProteomicsDB; 277760; -.
DR Antibodypedia; 25835; 468 antibodies from 34 providers.
DR DNASU; 13631; -.
DR Ensembl; ENSMUST00000047875; ENSMUSP00000046595; ENSMUSG00000035064.
DR Ensembl; ENSMUST00000106488; ENSMUSP00000102097; ENSMUSG00000035064.
DR Ensembl; ENSMUST00000106489; ENSMUSP00000102098; ENSMUSG00000035064.
DR GeneID; 13631; -.
DR KEGG; mmu:13631; -.
DR UCSC; uc009jnb.3; mouse.
DR CTD; 29904; -.
DR MGI; MGI:1195261; Eef2k.
DR VEuPathDB; HostDB:ENSMUSG00000035064; -.
DR eggNOG; ENOG502QVA3; Eukaryota.
DR GeneTree; ENSGT00940000157839; -.
DR HOGENOM; CLU_382143_0_0_1; -.
DR InParanoid; O08796; -.
DR OMA; LEAIITM; -.
DR OrthoDB; 741011at2759; -.
DR PhylomeDB; O08796; -.
DR TreeFam; TF316085; -.
DR BRENDA; 2.7.11.20; 3474.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR BioGRID-ORCS; 13631; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Eef2k; mouse.
DR PRO; PR:O08796; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O08796; protein.
DR Bgee; ENSMUSG00000035064; Expressed in ascending aorta and 235 other tissues.
DR ExpressionAtlas; O08796; baseline and differential.
DR Genevisible; O08796; MM.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
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:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0008135; F:translation factor activity, RNA binding; TAS:UniProtKB.
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; ISO:MGI.
DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; ISO:MGI.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:MGI.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0031952; P:regulation of protein autophosphorylation; IDA:UniProtKB.
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:UniProtKB.
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_0000086937"
FT DOMAIN 115..325
FT /note="Alpha-type protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00501"
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 359..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 419..474
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 27
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 61
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 347
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O00418"
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; by autocatalysis, RPS6KA1 and
FT RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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:21183079"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 473
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00418"
FT MOD_RES 499
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P70531"
SQ SEQUENCE 724 AA; 81739 MW; B892D7D547C8E7AE CRC64;
MADEDLIFCL EGVDGGRCSR AGHNADSDTD SDDDEGYFIC PITDDHMSNQ NVSSKVQSYY
SNLTKTECGS TGSPASSFHF KEAWKHAIEK AKHMPDPWAE FHLEDIATEH ATRHRYNAVT
GEWLKDEVLI KMASQPFGRG AMRECFRTKK LSNFLHAQQW KGASNYVAKR YIEPVDRSVY
FEDVQLQMEA KLWGEDYNRH KPPKQVDIMQ MCIIELKDRP GQPLFHLEHY IEGKYIKYNS
NSGFVRDDNI RLTPQAFSHF TFERSGHQLI VVDIQGVGDL YTDPQIHTEK GTDFGDGNLG
VRGMALFFYS HACNRICQSM GLTPFDLSPR EQDAVNQSTR LLQSAKTILR GTEEKCGSPR
IRTLSSSRPP LLLRLSENSG DENMSDVTFD SLPSSPSSAT PHSQKLDHLH WPVFGDLDNM
GPRDHDRMDN HRDSENSGDS GYPSEKRSDL DDPEPREHGH SNGNRRHESD EDSLGSSGRV
CVETWNLLNP SRLHLPRPSA VALEVQRLNA LDLGRKIGKS VLGKVHLAMV RYHEGGRFCE
KDEEWDRESA IFHLEHAADL GELEAIVGLG LMYSQLPHHI LADVSLKETE ENKTKGFDYL
LKAAEAGDRH SMILVARAFD TGLNLSPDRC QDWSEALHWY NTALETTDCD EGGEYDGIQD
EPQYALLARE AEMLLTGGFG LDKNPQRSGD LYTQAAEAAM EAMKGRLANQ YYEKAEEAWA
QMEE
