EEF2K

Summary

EEF2K (eukaryotic elongation factor 2 kinase, HGNC:24615) is a protein-coding gene on chromosome 16p12.2, encoding Eukaryotic elongation factor 2 kinase (O00418). Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation.

This gene encodes a highly conserved protein kinase in the calmodulin-mediated signaling pathway that links activation of cell surface receptors to cell division. This kinase is involved in the regulation of protein synthesis. It phosphorylates eukaryotic elongation factor 2 (EEF2) and thus inhibits the EEF2 function. The activity of this kinase is increased in many cancers and may be a valid target for anti-cancer treatment.

Source: NCBI Gene 29904 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 172 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_013302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24615
Approved symbol	EEF2K
Name	eukaryotic elongation factor 2 kinase
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	eEF-2K, CaMKIII
Ensembl gene	ENSG00000103319
Ensembl biotype	protein_coding
OMIM	606968
Entrez	29904

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000263026, ENST00000561791, ENST00000563555, ENST00000568269, ENST00000868084, ENST00000934427, ENST00000934428, ENST00000934429, ENST00000934430, ENST00000942056, ENST00000942057, ENST00000942058, ENST00000942059, ENST00000942060, ENST00000942061, ENST00000942062, ENST00000942063

RefSeq mRNA: 1 — MANE Select: NM_013302 NM_013302

CCDS: CCDS10604

Canonical transcript exons

ENST00000263026 — 18 exons

Exon	Start	End
ENSE00000676617	22244630	22244730
ENSE00000676618	22248755	22248815
ENSE00000676619	22250654	22250691
ENSE00000676621	22251151	22251322
ENSE00000676622	22256748	22256897
ENSE00000676623	22257253	22257385
ENSE00000676624	22257643	22257770
ENSE00000676629	22264818	22264880
ENSE00000676630	22266390	22266524
ENSE00000676631	22266688	22266876
ENSE00000676632	22273626	22273750
ENSE00000676633	22280198	22280376
ENSE00001319534	22225654	22225975
ENSE00001320569	22283887	22288738
ENSE00001384488	22206278	22206679
ENSE00003524859	22258494	22258695
ENSE00003595611	22260462	22260529
ENSE00003624097	22263110	22263187

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 93.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.5195 / max 384.1135, expressed in 1808 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153131	33.1733	1808
153132	0.3462	155

Top tissues by expression

138 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	93.78	gold quality
sural nerve	UBERON:0015488	93.73	gold quality
zone of skin	UBERON:0000014	93.44	gold quality
skin of abdomen	UBERON:0001416	92.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.04	gold quality
cerebellum	UBERON:0002037	89.97	gold quality
cerebellar cortex	UBERON:0002129	89.95	gold quality
cerebellar hemisphere	UBERON:0002245	89.94	gold quality
skeletal muscle tissue	UBERON:0001134	89.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.53	gold quality
mucosa of stomach	UBERON:0001199	88.50	gold quality
skeletal muscle organ	UBERON:0014892	88.45	gold quality
muscle of leg	UBERON:0001383	88.41	gold quality
gastrocnemius	UBERON:0001388	87.85	gold quality
prostate gland	UBERON:0002367	87.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.34	gold quality
muscle tissue	UBERON:0002385	87.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.06	gold quality
right uterine tube	UBERON:0001302	86.99	gold quality
popliteal artery	UBERON:0002250	86.80	gold quality
tibial artery	UBERON:0007610	86.79	gold quality
urinary bladder	UBERON:0001255	86.72	gold quality
endocervix	UBERON:0000458	85.88	gold quality
right coronary artery	UBERON:0001625	85.78	gold quality
adipose tissue	UBERON:0001013	85.56	gold quality
ectocervix	UBERON:0012249	85.48	gold quality
mammary gland	UBERON:0001911	85.47	gold quality
thoracic mammary gland	UBERON:0005200	85.47	gold quality
tibial nerve	UBERON:0001323	85.34	gold quality
uterine cervix	UBERON:0000002	85.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

189 targeting EEF2K, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487

Literature-anchored findings (GeneRIF, showing 40)

• our results suggest that anisomycin or TNF-alpha inhibit eEF2 kinase via the phosphorylation of Ser-359. (PMID:12171600)
• AMPK and eEF2 kinase may provide a key link between cellular energy status and the inhibition of protein synthesis, a major consumer of metabolic energy (PMID:14709557)
• Results show that eukaryotic elongation factor 2 kinase is a target for mTOR signaling independently of previously known downstream components of the pathway. (PMID:15024086)
• Levels of p-eEF2K were significantly increased, and total eEF2 significantly decreased in Alzheimer disease (PMID:16098202)
• These results suggest that eEF-2 kinase plays a regulatory role in the autophagic process in tumor cells and may promote cancer cell survival under conditions of nutrient deprivation. (PMID:16921268)
• These data closely match the control of Ser359 phosphorylation and indicate that cdc2 may be regulated by mTORC1. (PMID:18337751)
• The target cells (HGC-27) expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of gastric ulcer. (PMID:19636416)
• activation of eEF-2 kinase-mediated autophagy plays a protective role for cancer cells under metabolic stress conditions (PMID:20300520)
• results suggest that the expression of eEF-2 kinase contributes to migration and invasion of human glioma cells by protecting them from anoikis. (PMID:21278783)
• highly conserved residues in the C-terminal tip of eEF2K are essential for the phosphorylation of eEF2 (PMID:22115317)
• several autophosphorylation sites, including Thr(348), Thr(353), Ser(366) and Ser(445), all of which are highly conserved among vertebrate (PMID:22216903)
• Burn induces prolonged activation of eEF2K and eEF2 in pediatric patients. (PMID:22269896)
• Phosphorylation of Ser-500 lags behind the phosphorylation of Thr-348 and is associated with the Ca(2+)-independent activity of eEF-2K(eEF-2K) (PMID:22329831)
• These data indicate that eEF-2K is regulated at multiple levels with phosphorylation playing a critical role in the enzyme’s turnover under stressful conditions. (PMID:22749997)
• the disruption of eEF-2K expression in breast cancer cells results in the down-regulation of signaling pathways affecting growth, survival and resistance and has potential as a therapeutic approach for the treatment of breast cancer. (PMID:22911754)
• eEF-2 kinase fills critical niches in the life of a cancer cell and the eEF-2/eEF-2 kinase pathway is a key biochemical sensor. (PMID:22932089)
• EEF2 phosphorylation by cyclin A-cyclin-dependent kinase 2 (CDK2) on a novel site, serine 595 (S595), directly regulates T56 phosphorylation by eEF2K. (PMID:23184662)
• Data highlight a conserved role for eEF2K in protecting cells from nutrient deprivation and in conferring tumor cell adaptation to metabolic stress. (PMID:23706743)
• Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation. (PMID:23812389)
• down-regulation of eEF-2K leads to induction of intrinsic, extrinsic as well as AIF-dependent apoptosis. (PMID:24193916)
• The roles of specific residues, selected on the basis of structural data for MHCK A and TRPM7, in the function of eEF2K, is studied. (PMID:24732796)
• silencing of EEF2K promotes autophagic survival via activation of the AMPK-ULK1 pathway in colon cancer cells (PMID:24955726)
• eEF-2K activation appears to be analogous to an amplifier, where output volume may be controlled by either toggling the power switch or altering the volume control (PMID:25012662)
• mTORC1 pathway and the oncogenic Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) pathway cooperate to restrict eEF2K activity. (PMID:25182533)
• our results show, for the first time, that eEF-2K is involved in regulation of the invasive phenotype of PaCa cells through promoting a new signalling pathway, which is mediated by TG2/b1 integrin/Src/uPAR/MMP-2 (PMID:25215932)
• Deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K activity. (PMID:25330770)
• data show that the major trigger for activation of eEF2K upon mild cooling is the release of Ca2+ ions from the endoplasmic reticulum (ER) (PMID:25353634)
• data suggest that achieving an active conformation, rather than eEF2K activity per se, is required for its susceptibility to degradation. (PMID:25670349)
• Data show that eEF2K is activated during hypoxia or upon inhibition of prolyl hydroxylases and inhibited by its hydroxylation on a highly conserved proline residue, restricting its activity during normoxia. (PMID:25755286)
• Results show that eEF2K is rapidly activated in response to acidosis in cells, an effect that is followed by its downregulation. (PMID:25776553)
• Recent evidence shows that eEF2K plays an important role in learning and memory, processes that require the synthesis of new proteins and involve Ca-mediated signalling. eEF2K is activated under conditions of nutrient and energy depletion (PMID:26009171)
• Article reviews recent evidence concerning the role of eEF2K in human diseases; growing evidence links eEF2K to a range of human diseases, including cardiovascular conditions (atherosclerosis, via macrophage survival) and pulmonary arterial hypertension, as well as solid tumors, where eEF2K appears to play contrasting roles depending on tumor type and stage. eEF2K is also involved in neurological disorders. [Review] (PMID:26806303)
• Data suggest forkhead box M1 (FOXM1)/eukaryotic elongation factor 2 kinase (eEF2K) axis as a molecular target in breast and other cancers. (PMID:26918606)
• Results demonstrated that the promotive effect of eEF-2K on glycolysis resulted from the kinase-mediated restriction of synthesis of the protein phosphatase 2A-A (PP2A-A). (PMID:27181208)
• The structural basis for the recognition of EEF2K by calmodulin has been presented. (PMID:27499441)
• eEF2K activity is increased in postmortem Alzheimer’s disease (AD) patient cortex and hippocampus, and in the hippocampus of aged transgenic AD mice. eEF2K inhibition using pharmacological or genetic approaches prevented the toxic effects of Abeta42 oligomers on neuronal viability and dendrite formation in vitro. Findings highlight the potential utility of eEF2K inhibition to reduce Abeta-mediated oxidative stress in AD. (PMID:27752775)
• These new substrates suggest that eEF2K has a more diverse role in regulating cellular energy usage that involves multiple pathways and regulatory feedback. (PMID:27760376)
• This study reports how phosphorylation of a regulatory site (Ser-500) integrates with Ca(2+) and CaM to influence eEF-2K activity. (PMID:27956550)
• This study provides new insights into the control of eEF2K by AMPK. (PMID:28502587)
• Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis. (PMID:29024627)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef2k	ENSDARG00000035835
mus_musculus	Eef2k	ENSMUSG00000035064
rattus_norvegicus	Eef2k	ENSRNOG00000016448
caenorhabditis_elegans		WBGENE00001160

Paralogs (4): ALPK1 (ENSG00000073331), HSPA12B (ENSG00000132622), HSPA12A (ENSG00000165868), ALPK2 (ENSG00000198796)

Protein

Protein identifiers

Eukaryotic elongation factor 2 kinase — O00418 (reviewed: O00418)

Alternative names: Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase

All UniProt accessions (2): O00418, H3BRH4

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. Monomer or homodimer. Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity.

Post-translational modifications. Autophosphorylated at multiple residues, Thr-348 being the major site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-398 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-78 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-359 or RPS6KA1 and RPS6KB1 at Ser-366 instead decrease EEF2K activity and promote protein synthesis.

Activity regulation. Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.

Similarity. Belongs to the protein kinase superfamily. Alpha-type protein kinase family.

RefSeq proteins (1): NP_037434* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004166	a-kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR017400	eEF-2K	Family
IPR047588	eEF2K_a_kinase_dom	Domain
IPR051852	Alpha-type_PK	Family

Pfam: PF02816

Enzyme classification (BRENDA):

• EC 2.7.11.20 — elongation factor 2 kinase (BRENDA: 8 organisms, 62 substrates, 101 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• [translation elongation factor 2] + ATP = [translation elongation factor 2]-phosphate + ADP + H(+) (RHEA:21436)

UniProt features (92 total): modified residue 24, helix 21, strand 18, compositionally biased region 6, sequence variant 6, turn 5, region of interest 4, mutagenesis site 4, initiator methionine 1, chain 1, binding site 1, domain 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8GM4	X-RAY DIFFRACTION	2.12
8GM5	X-RAY DIFFRACTION	2.12
8FNY	X-RAY DIFFRACTION	2.22
9OCW	X-RAY DIFFRACTION	2.27
9PCQ	X-RAY DIFFRACTION	2.3
7SHQ	X-RAY DIFFRACTION	2.34
8FO6	X-RAY DIFFRACTION	2.55
5J8H	SOLUTION NMR
5KS5	SOLUTION NMR
6NX4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00418-F1	72.36	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 296–302

Post-translational modifications (24): 2, 18, 27, 61, 66, 70, 71, 72, 74, 78, 243, 348, 353, 359, 366, 392, 398, 435, 445, 470 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
78	decreased kinase activity.
348	decreased kinase activity.
366	abrogates phosphorylation by rps6kb1.
366	decreased kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-166208	mTORC1-mediated signalling

MSigDB gene sets: 289 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_DENDRITE_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (16): response to ischemia (GO:0002931), translational elongation (GO:0006414), myosin II filament disassembly (GO:0031037), cellular response to insulin stimulus (GO:0032869), negative regulation of apoptotic process (GO:0043066), positive regulation of endocytosis (GO:0045807), protein autophosphorylation (GO:0046777), positive regulation of synapse assembly (GO:0051965), positive regulation of dendritic spine morphogenesis (GO:0061003), cellular response to calcium ion (GO:0071277), cellular response to cAMP (GO:0071320), cellular response to anoxia (GO:0071454), regulation of translation at postsynapse (GO:0140245), cellular response to brain-derived neurotrophic factor stimulus (GO:1990416), response to prolactin (GO:1990637), protein phosphorylation (GO:0006468)

GO Molecular Function (11): protein kinase activity (GO:0004672), elongation factor-2 kinase activity (GO:0004686), calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), ATP binding (GO:0005524), translation factor activity, RNA binding (GO:0008135), nucleotide binding (GO:0000166), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), dendritic spine (GO:0043197), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
MTOR signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	3
postsynapse	2
cellular anatomical structure	2
response to stress	1
macromolecule biosynthetic process	1
myosin filament disassembly	1
myosin II filament organization	1
response to insulin	1
cellular response to peptide hormone stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
endocytosis	1
regulation of endocytosis	1
positive regulation of transport	1
positive regulation of cellular component organization	1
protein phosphorylation	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
positive regulation of neuron projection development	1
positive regulation of dendrite morphogenesis	1
dendritic spine morphogenesis	1
positive regulation of dendritic spine development	1
regulation of dendritic spine morphogenesis	1
response to calcium ion	1
cellular response to metal ion	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
cellular response to stress	1
response to anoxia	1
cellular response to decreased oxygen levels	1
regulation of translation at synapse	1
cellular response to nerve growth factor stimulus	1
response to peptide hormone	1
phosphorylation	1
protein modification process	1
kinase activity	1

Protein interactions and networks

STRING

1832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEF2K	EEF2	P13639	986
EEF2K	CALML3	P27482	871
EEF2K	CALML5	Q9NZT1	871
EEF2K	CALML6	Q8TD86	865
EEF2K	CALML4	Q96GE6	865
EEF2K	CALM1	P02593	840
EEF2K	RPS6KB1	P23443	797
EEF2K	EIF4B	P23588	796
EEF2K	PDCD4	Q53EL6	677
EEF2K	POLDIP3	Q9BY77	674
EEF2K	RPS6	P08227	665
EEF2K	PLCB1	Q9NQ66	653
EEF2K	EIF4E	P06730	640
EEF2K	MTOR	P42345	585
EEF2K	EIF4EBP1	Q13541	571

IntAct

19 interactions, top by confidence:

A	B	Type	Score
FBXW11	EEF2K	psi-mi:“MI:0914”(association)	0.640
FKBP6	EEF2K	psi-mi:“MI:0914”(association)	0.530
HSPA12B	EEF2K	psi-mi:“MI:0914”(association)	0.530
CDK1	EEF2K	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
EEF2K	CNOT1	psi-mi:“MI:0914”(association)	0.350
HSPA12B	VWA8	psi-mi:“MI:0914”(association)	0.350
SPRR1B	EEF2K	psi-mi:“MI:0914”(association)	0.350
EEF2K	RBP1	psi-mi:“MI:0914”(association)	0.350
COG2	EEF2K	psi-mi:“MI:0914”(association)	0.350
EEF2K	SRP14	psi-mi:“MI:0914”(association)	0.350
ACADVL	EEF2K	psi-mi:“MI:0914”(association)	0.350
CCNB1	EEF2K	psi-mi:“MI:0914”(association)	0.350
EEF2K	RPS6KB2	psi-mi:“MI:0217”(phosphorylation reaction)	0.310
RPS6KA1	EEF2K	psi-mi:“MI:0217”(phosphorylation reaction)	0.310
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (78): EEF2K (Affinity Capture-MS), EEF2K (Affinity Capture-MS), EEF2K (Affinity Capture-MS), EEF2K (Affinity Capture-MS), EEF2K (Proximity Label-MS), EEF2K (Affinity Capture-MS), EEF2K (Affinity Capture-MS), EEF2K (Proximity Label-MS), LOC101930123 (Proximity Label-MS), EEF2K (Affinity Capture-RNA), EEF2K (Proximity Label-MS), EEF2K (Reconstituted Complex), EEF2K (Reconstituted Complex), EEF2K (Affinity Capture-MS), EEF2K (Proximity Label-MS)

ESM2 similar proteins: A2AHJ4, A2AQW0, A7MBL8, A9JRL3, F1ND48, O00418, O08796, O08874, O35099, P15056, P28028, P32866, P34908, P53350, P53351, P62205, P70032, P70531, Q07832, Q16513, Q21029, Q2TA25, Q3TWN3, Q4U2V3, Q5E9N5, Q5R4L1, Q5R9R1, Q5ZKK7, Q62673, Q641K1, Q6DD21, Q6RI45, Q6ZN16, Q80V94, Q8AYK6, Q8BPM2, Q8IVH8, Q8QGV2, Q921C3, Q99683

Diamond homologs: O00418, O01991, O08796, P42527, P70531, P90648, Q54DK4, Q54SF9, Q6B9X6, Q8MY12, Q923J1, Q925B3, Q96QT4, Q9CXB8, Q8CIR4, Q9BX84, Q6FLI3, Q96QP1, Q86TB3, Q91ZB0, O95081, P52594, Q2TA45, Q4KLH5, Q80WC7, Q8K2K6, Q9FL69, A7T1N0, A8DYE2, J9SQF3, Q2TV84, Q2WEA5, Q7Z4N2, Q91YD4, Q93971, Q9HCF6, A2QP30, A7TNS8, P87060, Q924C5

SIGNOR signaling

37 interactions.

A	Effect	B	Mechanism
MAPK13	“down-regulates activity”	EEF2K	phosphorylation
RPS6KA1	“down-regulates activity”	EEF2K	phosphorylation
RPS6KB1	“down-regulates activity”	EEF2K	phosphorylation
CDK1	down-regulates	EEF2K	phosphorylation
MAPK13	down-regulates	EEF2K	phosphorylation
EEF2K	down-regulates	EEF2K	phosphorylation
FBXW11	down-regulates	EEF2K	ubiquitination
PRKAA1	up-regulates	EEF2K	phosphorylation
AMPK	up-regulates	EEF2K	phosphorylation
EEF2K	down-regulates	EEF2	phosphorylation
RPS6K	“down-regulates activity”	EEF2K	phosphorylation
CALM2	up-regulates	EEF2K	binding
CALM3	up-regulates	EEF2K	binding
mTORC1	“down-regulates activity”	EEF2K	phosphorylation
TRPM7	“up-regulates activity”	EEF2K	phosphorylation
CALM1	up-regulates	EEF2K	binding
MAPK14	“down-regulates activity”	EEF2K	phosphorylation
MAPKAPK5	unknown	EEF2K	phosphorylation
MAPKAPK3	unknown	EEF2K	phosphorylation
MAPKAPK2	unknown	EEF2K	phosphorylation
MAPK12	unknown	EEF2K	phosphorylation
PRKAA1	“up-regulates activity”	EEF2K	phosphorylation
PRKAA2	“up-regulates activity”	EEF2K	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

172 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	139
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625576	GRCh37/hg19 16p12.2(chr16:21884192-22288219)	Pathogenic

SpliceAI

4061 predictions. Top by Δscore:

Variant	Effect	Δscore
16:22206675:GGGAG:G	donor_gain	1.0000
16:22206676:GGAGG:G	donor_gain	1.0000
16:22225974:AGGT:A	donor_loss	1.0000
16:22225976:G:A	donor_loss	1.0000
16:22225976:G:GG	donor_gain	1.0000
16:22225977:T:A	donor_loss	1.0000
16:22244618:T:TA	acceptor_gain	1.0000
16:22244627:CA:C	acceptor_loss	1.0000
16:22244628:A:AG	acceptor_gain	1.0000
16:22244628:AG:A	acceptor_gain	1.0000
16:22244628:AGG:A	acceptor_loss	1.0000
16:22244629:G:GA	acceptor_gain	1.0000
16:22244629:GG:G	acceptor_gain	1.0000
16:22244629:GGA:G	acceptor_gain	1.0000
16:22244629:GGAA:G	acceptor_gain	1.0000
16:22244726:CACAG:C	donor_loss	1.0000
16:22244727:ACAGG:A	donor_loss	1.0000
16:22244728:CAGGT:C	donor_loss	1.0000
16:22244729:AGGTC:A	donor_loss	1.0000
16:22244730:GGTCA:G	donor_loss	1.0000
16:22244731:GTCAG:G	donor_loss	1.0000
16:22244732:T:A	donor_loss	1.0000
16:22250652:A:AG	acceptor_gain	1.0000
16:22250653:G:GG	acceptor_gain	1.0000
16:22250688:GGAC:G	donor_gain	1.0000
16:22250689:GAC:G	donor_gain	1.0000
16:22250689:GACG:G	donor_gain	1.0000
16:22250692:G:GG	donor_gain	1.0000
16:22251254:G:GT	donor_gain	1.0000
16:22251319:GCAG:G	donor_gain	1.0000

AlphaMissense

4831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:22244678:T:A	W99R	1.000
16:22244678:T:C	W99R	1.000
16:22244680:G:C	W99C	0.999
16:22244680:G:T	W99C	0.999
16:22250676:G:T	R144M	0.999
16:22250677:G:C	R144S	0.999
16:22250677:G:T	R144S	0.999
16:22251154:G:C	K150N	0.999
16:22251154:G:T	K150N	0.999
16:22251185:T:A	W161R	0.999
16:22251185:T:C	W161R	0.999
16:22251214:G:C	K170N	0.999
16:22251214:G:T	K170N	0.999
16:22251254:G:C	D184H	0.999
16:22251264:T:C	L187P	0.999
16:22251275:G:C	A191P	0.999
16:22256841:A:G	K238E	0.999
16:22256843:G:C	K238N	0.999
16:22256843:G:T	K238N	0.999
16:22257259:A:C	S259R	0.999
16:22257261:C:A	S259R	0.999
16:22257261:C:G	S259R	0.999
16:22257305:A:C	D274A	0.999
16:22257305:A:T	D274V	0.999
16:22257306:C:A	D274E	0.999
16:22257306:C:G	D274E	0.999
16:22257313:G:A	G277R	0.999
16:22257313:G:C	G277R	0.999
16:22257314:G:A	G277E	0.999
16:22257323:A:T	D280V	0.999

dbSNP variants (sampled 300 via entrez): RS1000002303 (16:22206676 G>A), RS1000004004 (16:22249351 G>A), RS1000139736 (16:22216538 CTG>C), RS1000203514 (16:22271545 A>C), RS1000219165 (16:22288054 T>G), RS1000257391 (16:22271942 C>T), RS1000426348 (16:22236738 G>A), RS1000454026 (16:22278585 A>G), RS1000476780 (16:22237309 A>G), RS1000492054 (16:22275218 T>G), RS1000554561 (16:22233444 C>T), RS1000645801 (16:22265571 G>A), RS1000661617 (16:22216664 C>G,T), RS1000706186 (16:22226993 G>A), RS1000728163 (16:22259272 G>A,T)

Disease associations

OMIM: gene MIM:606968 | disease phenotypes: MIM:136570

GenCC curated gene-disease

Mondo (1): chromosome 16p12.1 deletion syndrome, 520kb (MONDO:0007631)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006979_651	Heel bone mineral density	3.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565001	Fragile Site 16p12 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5026 (SINGLE PROTEIN), CHEMBL6193782 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,497 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1672002	THYMOQUINONE	2	1,497

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — eEF2K subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 34 [PMID: 20189382]	Inhibition	6.77	pIC50

Binding affinities (BindingDB)

43 measured of 50 human assays (50 total across all organisms); most potent 43 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-amino-8,8-dimethyl-4-(1,3-thiazol-5-yl)-6,7-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	300 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(1,3-thiazol-5-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-7,7-dimethyl-4-(1,3-thiazol-5-yl)-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-5,7,7-trimethyl-4-(1,3-thiazol-5-yl)-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(4-methyl-1,3-thiazol-5-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(2,4-dimethyl-1,3-thiazol-5-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	500 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(1-methylpyrazol-4-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	700 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(4-bromothiophen-2-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	800 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(3-bromothiophen-2-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	800 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-thiophen-3-yl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	900 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(4-bromofuran-2-yl)-8,8-dimethyl-6,7-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	900 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
7-amino-9-(1,3-thiazol-5-yl)-5-thia-3-azatetracyclo[9.2.1.02,10.04,8]tetradeca-2(10),3,6,8-tetraene-6-carboxamide	IC50	900 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(furan-2-yl)-7,7-dimethyl-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-butan-2-yl-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	1000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(5-chlorofuran-2-yl)-6,6-dimethyl-7,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1100 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(furan-3-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	1100 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-cyclopropyl-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	1100 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-6,6-dimethyl-4-(1,3-thiazol-5-yl)-7,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1100 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(furan-2-yl)-6,6-dimethyl-7,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1200 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(5-chlorothiophen-2-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	1400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-8,8-dimethyl-4-(1-methylpyrazol-4-yl)-6,7-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(5-bromothiophen-2-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	1500 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(5-chlorofuran-2-yl)-7,7-dimethyl-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1600 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(furan-3-yl)-6,6-dimethyl-7,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	2000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(1,3-thiazol-2-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	2000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-6,6-dimethyl-4-thiophen-3-yl-7,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	2200 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(5-chlorofuran-2-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	2400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-8-(furan-2-yl)-12,12-dimethyl-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	2500 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
(8E)-3-amino-4-(5-chlorofuran-2-yl)-8-[(5-chlorofuran-2-yl)methylidene]-6,6-dimethyl-5,7-dihydrothieno[2,3-b]quinoline-2-carboxamide	IC50	2700 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(1,3-thiazol-5-yl)spiro[6,7-dihydro-5H-thieno[2,3-b]quinoline-8,1’-cyclopentane]-2-carboxamide	IC50	3100 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(1,3-thiazol-4-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	3400 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(1,3-oxazol-4-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	3500 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
6-amino-12,12-dimethyl-8-(4-methyl-1,3-thiazol-2-yl)-4-thia-2-azatricyclo[7.3.0.03,7]dodeca-1,3(7),5,8-tetraene-5-carboxamide	IC50	3800 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(furan-2-yl)-5,7,7-trimethyl-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	4600 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(5-chlorofuran-2-yl)-8,8-dimethyl-6,7-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	4700 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(5-chlorofuran-2-yl)-5,7,7-trimethyl-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	5000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
(8E)-3-amino-4-(5-chlorofuran-2-yl)-8-[(5-chlorofuran-2-yl)methylidene]-6-propyl-6,7-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	6000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
(8E)-3-amino-4-(furan-3-yl)-8-(furan-3-ylmethylidene)-6,6-dimethyl-5,7-dihydrothieno[2,3-b]quinoline-2-carboxamide	IC50	6000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(3,4-dichlorophenyl)-7,7-dimethyl-6,8-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	23000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(5-chlorofuran-2-yl)-8-phenyl-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide	IC50	31000 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
(8E)-3-amino-4-(3-chloro-2-fluorophenyl)-8-[(3-chloro-2-fluorophenyl)methylidene]-6,6-dimethyl-5,7-dihydrothieno[2,3-b]quinoline-2-carboxamide	IC50	5.02e+06 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
(8E)-3-amino-4-(5-chlorofuran-2-yl)-8-[(5-chlorofuran-2-yl)methylidene]-6-phenyl-6,7-dihydro-5H-thieno[2,3-b]quinoline-2-carboxamide	IC50	1e+07 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity
3-amino-4-(5-chlorofuran-2-yl)-6-phenyl-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide	IC50	1e+07 nM	US-10106552: Compounds inhibiting eukaryotic elongation factor 2 kinase activity

ChEMBL bioactivities

121 potent at pChembl≥5 of 150 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.50	IC50	32	nM	CHEMBL5174034
7.22	IC50	60	nM	CHEMBL4171806
7.22	IC50	60	nM	CHEMBL1683636
7.16	IC50	69	nM	CHEMBL5204448
7.10	Ki	79.43	nM	CHEMBL1988173
6.96	IC50	110	nM	CHEMBL1094018
6.77	IC50	170	nM	CHEMBL1092820
6.66	IC50	220	nM	CHEMBL1091317
6.64	IC50	230	nM	CHEMBL5194579
6.55	IC50	280	nM	CHEMBL1977874
6.55	IC50	280	nM	CHEMBL1094026
6.52	IC50	300	nM	CHEMBL5969570
6.52	IC50	300	nM	CHEMBL1089019
6.51	IC50	310	nM	CHEMBL4776943
6.50	IC50	320	nM	CHEMBL1091829
6.48	Kd	330	nM	CHEMBL5593199
6.48	IC50	330	nM	CHEMBL1091074
6.46	IC50	350	nM	CHEMBL1091450
6.40	IC50	400	nM	CHEMBL5838926
6.40	IC50	400	nM	CHEMBL6018015
6.40	IC50	400	nM	CHEMBL5742447
6.40	IC50	400	nM	CHEMBL6054368
6.40	Ki	398.1	nM	CHEMBL1989805
6.38	IC50	420	nM	CHEMBL1977874
6.36	IC50	440	nM	CHEMBL437612
6.36	Kd	436	nM	CHEMBL5590973
6.34	IC50	460	nM	CHEMBL1091830
6.31	Kd	492	nM	CHEMBL5592236
6.30	IC50	500	nM	CHEMBL5834926
6.29	IC50	510	nM	CHEMBL1977874
6.19	IC50	640	nM	CHEMBL1094038
6.18	IC50	660	nM	CHEMBL1091075
6.16	IC50	700	nM	CHEMBL5956124
6.12	IC50	762	nM	CHEMBL4281348
6.12	IC50	760	nM	CHEMBL4281348
6.10	IC50	800	nM	CHEMBL5744883
6.10	IC50	800	nM	CHEMBL5836464
6.10	IC50	800	nM	CHEMBL1091459
6.10	Ki	794.3	nM	CHEMBL2006263
6.10	Ki	794.3	nM	CHEMBL1977874
6.07	IC50	860	nM	CHEMBL1089016
6.07	IC50	860	nM	CHEMBL1090045
6.05	IC50	900	nM	CHEMBL5873351
6.05	IC50	900	nM	CHEMBL5775344
6.05	IC50	900	nM	CHEMBL6062707
6.03	IC50	930	nM	CHEMBL3327225
6.03	IC50	940	nM	CHEMBL1089330
6.00	IC50	1000	nM	CHEMBL3326370
6.00	IC50	1000	nM	CHEMBL5999230
6.00	IC50	1000	nM	CHEMBL5908345

PubChem BioAssay actives

62 with measured affinity, of 904 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-benzyl-N-(2,4-difluorophenyl)-1,4-diazepane-1-carboxamide	1891906: Inhibition of eEF2K (unknown origin)	ic50	0.0320	uM
1-benzyl-3-hexadecyl-2-methylimidazol-1-ium iodide	1703947: Inhibition of eEF2K (unknown origin)	ic50	0.0600	uM
1-benzyl-3-hexadecyl-2-methyl-4,5-dihydroimidazol-1-ium iodide	1348545: Inhibition of N-terminal GST-tagged recombinant human eEF2K expressed in Escherichia coli using biotinylated myelin basic protein as substrate after 45 mins in presence of [gamma-33P]-ATP by scintillation counting method	ic50	0.0600	uM
1-chloro-4-[1-(4-chlorophenyl)sulfonylcyclopropyl]sulfonylbenzene	1891906: Inhibition of eEF2K (unknown origin)	ic50	0.0690	uM
2-(4-chlorophenyl)-10-thia-5,7,12-triazatetracyclo[11.7.0.03,11.04,9]icosa-1(13),2,4(9),5,7,11-hexaen-8-amine	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.1100	uM
6-amino-8-(furan-2-yl)-4-thia-2-azatricyclo[7.7.0.03,7]hexadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.1700	uM
8-morpholin-4-yl-11-thia-9,14,16-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-1,7,9,12,14,16-hexaen-13-amine	1891906: Inhibition of eEF2K (unknown origin)	ic50	0.2200	uM
3-phenyl-7-pyrrolidin-1-yl-2,3-dihydroinden-1-one	1891906: Inhibition of eEF2K (unknown origin)	ic50	0.2300	uM
7-amino-1-cyclopropyl-3-ethyl-2,4-dioxopyrido[2,3-d]pyrimidine-6-carboxamide	1184696: ATP competitive inhibition of human eEF-2K using 5 uM ATP	ic50	0.2800	uM
6-amino-8-(5-chlorofuran-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.2800	uM
6-amino-8-[5-(trifluoromethyl)furan-2-yl]-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.3000	uM
4-methyl-2-(4-methylphenyl)-6-propan-2-yl-5,6-dihydro-1,3-selenazin-4-ol	1703947: Inhibition of eEF2K (unknown origin)	ic50	0.3100	uM
6-amino-8-[(E)-2-(furan-2-yl)ethenyl]-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.3200	uM
4-benzyl-2-(3,4-dimethylphenyl)-6-(piperidine-1-carbonyl)-1,2,4-triazine-3,5-dione	2118055: Binding affinity to eEF2K (unknown origin) assessed as dissociation constant measured by SPR analysis	kd	0.3300	uM
6-amino-8-(1-benzofuran-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.3300	uM
2-(furan-2-yl)-10-thia-5,7,12-triazatetracyclo[11.7.0.03,11.04,9]icosa-1(13),2,4(9),5,7,11-hexaen-8-amine	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.3500	uM
tert-butyl N-[[1-[2-(3,4-dimethylphenyl)-4-[(3-fluorophenyl)methyl]-3,5-dioxo-1,2,4-triazine-6-carbonyl]piperidin-3-yl]methyl]carbamate	2118055: Binding affinity to eEF2K (unknown origin) assessed as dissociation constant measured by SPR analysis	kd	0.4360	uM
2-[(4-hydroxy-3,5-dimethylphenyl)methylidene]cyclopent-4-ene-1,3-dione	1348544: Inhibition of eEF2K in human A431 cells using eEF2 as substrate preincubated for 30 mins followed by ATP/[gamma-32P]-ATP addition measured after 10 mins	ic50	0.4400	uM
6-amino-8-(3-methylthiophen-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.4600	uM
4-benzyl-2-(3,4-dimethylphenyl)-3,5-dioxo-N-(2-pyrrolidin-1-ylethyl)-1,2,4-triazine-6-carboxamide	2118055: Binding affinity to eEF2K (unknown origin) assessed as dissociation constant measured by SPR analysis	kd	0.4920	uM
6-amino-8-(furan-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.6400	uM
6-amino-8-(5-ethylfuran-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.6600	uM
1-(3-chlorophenyl)-3-[4-[2-(ethylamino)-4-pyridinyl]-3-(trifluoromethyl)phenyl]urea	1891906: Inhibition of eEF2K (unknown origin)	ic50	0.7600	uM
6-amino-8-[5-(hydroxymethyl)furan-2-yl]-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.8000	uM
6-amino-8-(2-methylpropyl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.8600	uM
4-(6-amino-5-carbamoyl-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraen-8-yl)benzoic acid	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.8600	uM
7-amino-1-cyclopropyl-2,4-dioxo-3-propylpyrido[2,3-d]pyrimidine-6-carboxamide	1184697: Inhibition of human recombinant eEF-2K expressed in bacteria pre-incubated for 30 mins before adding peptide substrate and [gamma32P]ATP by scintillation counting method	ic50	0.9300	uM
6-amino-8-pyridin-3-yl-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.9400	uM
6-amino-8-(3,4-dichlorophenyl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.9900	uM
6-amino-8-(1-methylpyrrol-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	0.9900	uM
7-amino-1,3-diethyl-2,4-dioxopyrido[2,3-d]pyrimidine-6-carboxamide	1184697: Inhibition of human recombinant eEF-2K expressed in bacteria pre-incubated for 30 mins before adding peptide substrate and [gamma32P]ATP by scintillation counting method	ic50	1.0000	uM
6-amino-8-methyl-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1,3(7),5,8-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.1000	uM
6-amino-8-(4-chlorophenyl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.1000	uM
6-amino-8-(furan-3-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.1000	uM
6-amino-8-(4,5-dimethylfuran-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.1000	uM
6-amino-8-(furan-2-yl)-4-thia-2-azatricyclo[7.5.0.03,7]tetradeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.1000	uM
6-amino-8-(3-methylphenyl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.2000	uM
6-amino-8-(2-fluoro-5-methoxyphenyl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.3000	uM
6-amino-8-(1,3-thiazol-2-yl)-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	1.4000	uM
6-amino-8-cyclopropyl-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1(9),2,5,7-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	2.0000	uM
6-amino-4-thia-2-azatricyclo[7.6.0.03,7]pentadeca-1,3(7),5,8-tetraene-5-carboxamide	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	2.5000	uM
2-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]cyclopent-4-ene-1,3-dione	325786: Inhibition of eEF2 kinase	ic50	3.2000	uM
10-thia-5,7,12-triazatetracyclo[11.7.0.03,11.04,9]icosa-1,3(11),4(9),5,7,12-hexaen-8-amine	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	3.7000	uM
10-(furan-2-yl)-18-thia-2,13,15-triazatetracyclo[9.7.0.03,9.012,17]octadeca-1,3(9),10,12(17),13,15-hexaen-16-amine	473724: Inhibition of GST tagged eEf2K expressed in Escherichia coli by fluorometric method	ic50	4.7000	uM
(E)-1-[6-[(3-acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2,2-dimethylchromen-8-yl]-3-phenylprop-2-en-1-one	1703947: Inhibition of eEF2K (unknown origin)	ic50	5.3000	uM
3-[(4-cyanophenyl)sulfonylamino]-3-(2,4-dichlorophenyl)propanoic acid	1348503: Inhibition of eEF2K (unknown origin) using peptide MH-1 as substrate after 2 hrs by ADP-Glo luminescent assay	ic50	5.5000	uM
7-amino-1-cyclopropyl-3-methyl-2,4-dioxopyrido[2,3-d]pyrimidine-6-carboxamide	1184697: Inhibition of human recombinant eEF-2K expressed in bacteria pre-incubated for 30 mins before adding peptide substrate and [gamma32P]ATP by scintillation counting method	ic50	6.1000	uM
7-amino-1-cyclopropyl-2,4-dioxopyrido[2,3-d]pyrimidine-6-carboxamide	1184697: Inhibition of human recombinant eEF-2K expressed in bacteria pre-incubated for 30 mins before adding peptide substrate and [gamma32P]ATP by scintillation counting method	ic50	6.6000	uM
2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione	1924150: Inhibition of eEF2K (unknown origin) by western blot analysis	ic50	8.2000	uM
3-(2,4-dichlorophenyl)-3-[[4-(trifluoromethyl)phenyl]sulfonylamino]propanoic acid	1348503: Inhibition of eEF2K (unknown origin) using peptide MH-1 as substrate after 2 hrs by ADP-Glo luminescent assay	ic50	9.5000	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	7
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
sulforaphane	decreases expression	1
tanshinone II A sodium sulfonate	decreases phosphorylation, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
hydroquinone	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
azoxystrobin	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

266 unique, capped per target: 265 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004134	Binding	Inhibition of EFK2 at 1 uM relative to control	Novel potent BRAF inhibitors: toward 1 nM compounds through optimization of the central phenyl ring. — J Med Chem
CHEMBL1963711	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: EEF2K	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E0CB	Ubigene HeLa EEF2K KO	Cancer cell line	Female
CVCL_RR01	MCF10A EEF2K (-/-)	Spontaneously immortalized cell line	Female
CVCL_SL46	HAP1 EEF2K (-) 1	Cancer cell line	Male
CVCL_SL47	HAP1 EEF2K (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.