UniProtKB - P70531 (EF2K_RAT)
Protein
Eukaryotic elongation factor 2 kinase
Gene
Eef2k
Organism
Rattus norvegicus (Rat)
Status
Functioni
Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced (By similarity).By similarity
Catalytic activityi
- EC:2.7.11.20
Activity regulationi
Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 295 – 301 | ATPBy similarity | 7 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium ion binding Source: InterPro
- calmodulin binding Source: UniProtKB
- elongation factor-2 kinase activity Source: RGD
GO - Biological processi
- cellular response to anoxia Source: RGD
- cellular response to brain-derived neurotrophic factor stimulus Source: RGD
- cellular response to calcium ion Source: RGD
- cellular response to cAMP Source: RGD
- cellular response to insulin stimulus Source: RGD
- negative regulation of apoptotic process Source: RGD
- positive regulation of dendritic spine morphogenesis Source: RGD
- positive regulation of endocytosis Source: RGD
- positive regulation of synapse assembly Source: RGD
- protein autophosphorylation Source: UniProtKB
- regulation of protein autophosphorylation Source: RGD
- response to ischemia Source: RGD
- response to prolactin Source: RGD
Keywordsi
Molecular function | Calmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Calcium, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.20, 5301 |
Reactomei | R-RNO-166208, mTORC1-mediated signalling |
Names & Taxonomyi
Protein namesi | Recommended name: Eukaryotic elongation factor 2 kinase (EC:2.7.11.20)Short name: eEF-2 kinase Short name: eEF-2K Alternative name(s): Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase |
Gene namesi | Name:Eef2k |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 2538, Eef2k |
Subcellular locationi
Other locations
- dendritic spine Source: SynGO-UCL
- postsynaptic density Source: RGD
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000086938 | 2 – 724 | Eukaryotic elongation factor 2 kinaseAdd BLAST | 723 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineBy similarity | 1 | |
Modified residuei | 18 | PhosphoserineBy similarity | 1 | |
Modified residuei | 27 | PhosphoserineBy similarity | 1 | |
Modified residuei | 70 | PhosphoserineBy similarity | 1 | |
Modified residuei | 73 | PhosphoserineCombined sources | 1 | |
Modified residuei | 77 | Phosphoserine; by autocatalysis and TRPM7By similarity | 1 | |
Modified residuei | 242 | PhosphoserineBy similarity | 1 | |
Modified residuei | 347 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 352 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 358 | Phosphoserine; by MAPK13 and CDK1By similarity | 1 | |
Modified residuei | 365 | PhosphoserineCombined sources | 1 | |
Modified residuei | 391 | PhosphoserineBy similarity | 1 | |
Modified residuei | 397 | Phosphoserine; by AMPKBy similarity | 1 | |
Modified residuei | 434 | PhosphoserineBy similarity | 1 | |
Modified residuei | 444 | PhosphoserineCombined sources | 1 | |
Modified residuei | 469 | PhosphoserineCombined sources | 1 | |
Modified residuei | 473 | PhosphoserineCombined sources | 1 | |
Modified residuei | 476 | PhosphoserineCombined sources | 1 | |
Modified residuei | 499 | Phosphoserine; by PKA1 Publication | 1 |
Post-translational modificationi
The N-terminus is blocked.
Autophosphorylated at multiple residues, Thr-347 being the major site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-397 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-77 resulting in improved protein stability, higher EE2F phosphorylated and subsequently reduced rate of protein synthesis. Phosphorylation by other kinases such as CDK1 and MAPK13 at Ser-358 or RPS6KA1 and RPS6KB1 at Ser-365 instead decrease EEF2K activity and promote protein synthesis (By similarity).By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
PaxDbi | P70531 |
PRIDEi | P70531 |
PTM databases
iPTMneti | P70531 |
PhosphoSitePlusi | P70531 |
Expressioni
Tissue specificityi
Widely expressed, with high levels in reticulocytes and skeletal muscle.1 Publication
Gene expression databases
Bgeei | ENSRNOG00000016448, Expressed in skeletal muscle tissue and 22 other tissues |
Genevisiblei | P70531, RN |
Interactioni
Subunit structurei
Monomer or homodimer (Probable).
Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (By similarity).
By similarityCuratedGO - Molecular functioni
- calmodulin binding Source: UniProtKB
Protein-protein interaction databases
ELMi | P70531 |
STRINGi | 10116.ENSRNOP00000022726 |
Chemistry databases
BindingDBi | P70531 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 115 – 325 | Alpha-type protein kinasePROSITE-ProRule annotationAdd BLAST | 211 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 80 – 93 | Calmodulin-bindingBy similarityAdd BLAST | 14 |
Domaini
The catalytic domain is located to N-terminal region. The neighbor region contains the calmodulin-binding domain (By similarity).By similarity
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QVA3, Eukaryota |
GeneTreei | ENSGT00940000157839 |
HOGENOMi | CLU_382143_0_0_1 |
InParanoidi | P70531 |
OMAi | HWPVFGD |
OrthoDBi | 741011at2759 |
PhylomeDBi | P70531 |
TreeFami | TF316085 |
Family and domain databases
Gene3Di | 1.25.40.10, 1 hit |
InterProi | View protein in InterPro IPR017400, eEF-2K IPR011009, Kinase-like_dom_sf IPR004166, MHCK_EF2_kinase IPR006597, Sel1-like IPR011990, TPR-like_helical_dom_sf |
Pfami | View protein in Pfam PF02816, Alpha_kinase, 1 hit PF08238, Sel1, 4 hits |
PIRSFi | PIRSF038139, Elongation_factor_2_kinase, 1 hit |
SMARTi | View protein in SMART SM00811, Alpha_kinase, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51158, ALPHA_KINASE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P70531-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MADEDLIFRL EGVDGGGSSG AGRHGDSDTD SDDDEGYFIC PITDDHMSNQ
60 70 80 90 100
NVNSKGQGYY NNLLKTECGS TGSPASSFHF KEAWKHAIEK AKHMPDPWAE
110 120 130 140 150
FHLEDIATEH ATRHRYNAVT GEWLKDEVLI KMASQPFGRG AMRECFRTKK
160 170 180 190 200
LSNFLHAQHW KGASNYVAKR YLEPVDRSVY FEDVQLQMEA KLWGEEYNRH
210 220 230 240 250
KPPKQVDIMQ MCIIELKDRQ GQPLFHLEHY IEGKYIKYNS NSGFVRDDNI
260 270 280 290 300
RLTPQAFSHF TFERSGHQLI VVDIQGVGDL YTDPQIHTEK GTDFGDGNLG
310 320 330 340 350
VRGMALFFYS HACNRICQSM GLAPFDLSPR EQDAVNQSTK LLQSAKTILR
360 370 380 390 400
GTEEKCGSPR IRTLSGSRPP LLLRLSENSG DENMSDVTFD SLPSSPSSAT
410 420 430 440 450
PHSQKLDHLH WPVFGDLDNM GPRDHDRMDN HRDSENSGDS GYPSEKRSDL
460 470 480 490 500
DDPEPREHGH SNGNRRPESD EDSLGSSGRV CVETWNLLNP SRLHLPRPSA
510 520 530 540 550
VALEVQRLNA LDLGRKIGKS VLGKVHLAMV RYHEGGRFCE KDEEWDQESA
560 570 580 590 600
IFHLEHAADL GELEAIVGLG LMYSQLPHHI LADVSLEETE ENKTKGFDYL
610 620 630 640 650
LKAAEAGDRQ SMILVARAFD TGLNLSPDRC QDWSEALHWY NTALETTDCD
660 670 680 690 700
EGGEYDGIQD EPQYALLARE AEMLLTGGFG LDKNPQRSGD LYTQAAEAAM
710 720
EAMKGRLANQ YYEKAEEAWA QMEE
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X96426 mRNA Translation: CAA65286.1 U93849 mRNA Translation: AAB58272.1 |
RefSeqi | NP_037079.1, NM_012947.2 XP_006230218.1, XM_006230156.3 XP_006230219.1, XM_006230157.3 XP_006230220.1, XM_006230158.3 |
Genome annotation databases
Ensembli | ENSRNOT00000022726; ENSRNOP00000022726; ENSRNOG00000016448 |
GeneIDi | 25435 |
KEGGi | rno:25435 |
UCSCi | RGD:2538, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X96426 mRNA Translation: CAA65286.1 U93849 mRNA Translation: AAB58272.1 |
RefSeqi | NP_037079.1, NM_012947.2 XP_006230218.1, XM_006230156.3 XP_006230219.1, XM_006230157.3 XP_006230220.1, XM_006230158.3 |
3D structure databases
SMRi | P70531 |
ModBasei | Search... |
Protein-protein interaction databases
ELMi | P70531 |
STRINGi | 10116.ENSRNOP00000022726 |
Chemistry databases
BindingDBi | P70531 |
ChEMBLi | CHEMBL3325307 |
PTM databases
iPTMneti | P70531 |
PhosphoSitePlusi | P70531 |
Proteomic databases
PaxDbi | P70531 |
PRIDEi | P70531 |
Genome annotation databases
Ensembli | ENSRNOT00000022726; ENSRNOP00000022726; ENSRNOG00000016448 |
GeneIDi | 25435 |
KEGGi | rno:25435 |
UCSCi | RGD:2538, rat |
Organism-specific databases
CTDi | 29904 |
RGDi | 2538, Eef2k |
Phylogenomic databases
eggNOGi | ENOG502QVA3, Eukaryota |
GeneTreei | ENSGT00940000157839 |
HOGENOMi | CLU_382143_0_0_1 |
InParanoidi | P70531 |
OMAi | HWPVFGD |
OrthoDBi | 741011at2759 |
PhylomeDBi | P70531 |
TreeFami | TF316085 |
Enzyme and pathway databases
BRENDAi | 2.7.11.20, 5301 |
Reactomei | R-RNO-166208, mTORC1-mediated signalling |
Miscellaneous databases
PROi | PR:P70531 |
Gene expression databases
Bgeei | ENSRNOG00000016448, Expressed in skeletal muscle tissue and 22 other tissues |
Genevisiblei | P70531, RN |
Family and domain databases
Gene3Di | 1.25.40.10, 1 hit |
InterProi | View protein in InterPro IPR017400, eEF-2K IPR011009, Kinase-like_dom_sf IPR004166, MHCK_EF2_kinase IPR006597, Sel1-like IPR011990, TPR-like_helical_dom_sf |
Pfami | View protein in Pfam PF02816, Alpha_kinase, 1 hit PF08238, Sel1, 4 hits |
PIRSFi | PIRSF038139, Elongation_factor_2_kinase, 1 hit |
SMARTi | View protein in SMART SM00811, Alpha_kinase, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51158, ALPHA_KINASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | EF2K_RAT | |
Accessioni | P70531Primary (citable) accession number: P70531 Secondary accession number(s): O09089 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | February 1, 1997 | |
Last modified: | December 2, 2020 | |
This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families