EEF2

Summary

EEF2 (eukaryotic translation elongation factor 2, HGNC:3214) is a protein-coding gene on chromosome 19p13.3, encoding Elongation factor 2 (P13639). Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

This gene encodes a member of the GTP-binding translation elongation factor family. This protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome. This protein is completely inactivated by EF-2 kinase phosporylation.

Source: NCBI Gene 1938 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia type 26 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 573 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3214
Approved symbol	EEF2
Name	eukaryotic translation elongation factor 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	EEF-2
Ensembl gene	ENSG00000167658
Ensembl biotype	protein_coding
OMIM	130610
Entrez	1938

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000309311, ENST00000594885, ENST00000596417, ENST00000598182, ENST00000598436, ENST00000600720, ENST00000600794, ENST00000858184, ENST00000858185, ENST00000858186, ENST00000858187, ENST00000858188, ENST00000858189, ENST00000858190, ENST00000858191, ENST00000939490, ENST00000939491, ENST00000939492, ENST00000939493, ENST00000939494, ENST00000939495, ENST00000939496, ENST00000939497, ENST00000967316, ENST00000967317, ENST00000967318, ENST00000967319

RefSeq mRNA: 1 — MANE Select: NM_001961 NM_001961

CCDS: CCDS12117

Canonical transcript exons

ENST00000309311 — 15 exons

Exon	Start	End
ENSE00001115364	3979808	3980066
ENSE00001115367	3980514	3980709
ENSE00001115368	3977215	3977347
ENSE00001115369	3976056	3976747
ENSE00001115371	3977819	3978172
ENSE00001115372	3982246	3982424
ENSE00001115375	3983110	3983291
ENSE00001115376	3982807	3983018
ENSE00001265516	3977428	3977610
ENSE00001265527	3979329	3979436
ENSE00001316318	3980841	3980979
ENSE00003201519	3985378	3985463
ENSE00003535069	3981947	3982052
ENSE00003544486	3984136	3984350
ENSE00003617697	3981339	3981452

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1535.7522 / max 12245.0284, expressed in 1828 samples.

FANTOM5 promoters (32 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178393	1455.7706	1828
178376	10.2836	1728
178384	6.7439	1736
178377	5.7653	1616
178368	5.0148	1426
178366	4.8812	1541
178379	3.3904	1478
178358	3.3155	1434
178364	3.1947	1486
178375	2.9880	1482

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.96	gold quality
cartilage tissue	UBERON:0002418	99.90	gold quality
stromal cell of endometrium	CL:0002255	99.87	gold quality
lateral globus pallidus	UBERON:0002476	99.87	gold quality
corpus epididymis	UBERON:0004359	99.84	gold quality
cortical plate	UBERON:0005343	99.84	gold quality
adult organism	UBERON:0007023	99.84	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.82	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.82	gold quality
caput epididymis	UBERON:0004358	99.82	gold quality
endometrium epithelium	UBERON:0004811	99.82	gold quality
cervix squamous epithelium	UBERON:0006922	99.82	gold quality
colonic epithelium	UBERON:0000397	99.81	gold quality
calcaneal tendon	UBERON:0003701	99.81	gold quality
germinal epithelium of ovary	UBERON:0001304	99.80	gold quality
mammary duct	UBERON:0001765	99.80	gold quality
substantia nigra pars compacta	UBERON:0001965	99.80	gold quality
nipple	UBERON:0002030	99.80	gold quality
type B pancreatic cell	CL:0000169	99.79	gold quality
cardia of stomach	UBERON:0001162	99.79	gold quality
epithelium of mammary gland	UBERON:0003244	99.79	gold quality
tendon	UBERON:0000043	99.78	gold quality
penis	UBERON:0000989	99.78	gold quality
ventricular zone	UBERON:0003053	99.78	gold quality
ganglionic eminence	UBERON:0004023	99.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.77	gold quality
embryo	UBERON:0000922	99.76	gold quality
tibia	UBERON:0000979	99.76	gold quality
mammalian vulva	UBERON:0000997	99.76	gold quality
gastrocnemius	UBERON:0001388	99.76	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3481.92
E-HCAD-4	yes	3148.78
E-MTAB-6701	yes	116.41
E-HCAD-1	yes	104.63
E-CURD-122	yes	89.92
E-CURD-88	yes	54.77
E-HCAD-11	yes	48.29
E-GEOD-134144	yes	36.90
E-MTAB-9543	yes	29.87
E-MTAB-9221	yes	17.61
E-MTAB-10553	yes	16.61
E-MTAB-10042	yes	10.76
E-HCAD-35	yes	7.18
E-MTAB-9801	yes	5.73
E-MTAB-8884	no	2550.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

24 targeting EEF2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-2114-5P	96.00	64.56	617
HSA-MIR-584-5P	95.82	68.05	848
HSA-MIR-3131	95.33	65.74	102
HSA-MIR-758-5P	93.99	64.46	534
HSA-MIR-611	93.79	64.24	81
HSA-MIR-4765	93.11	66.17	737

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• inhibition of protein synthesis under high pressure occurs independent of the phosphorylation of eEF-2 (PMID:15534876)
• Levels of p-eEF2K were significantly increased, and total eEF2 significantly decreased in Alzheimer disease (PMID:16098202)
• Data show that overproduction of elongation factor 2 blocks HIV-1 viral protein R-induced cell death both in fission yeast and human cells. (PMID:16520893)
• Hypoxia inhibits protein synthesis through a 4EBP1 and EEF2 pathway controlled by mTOR and unbcoupled in breast cancer cells. (PMID:16648488)
• Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type. (PMID:19036825)
• Overexpressed eEF2 in gastrointestinal cancers promoted G2/M progression and enhanced their cell growth in vitro and in vivo. (PMID:19360331)
• melanoma antigen expressed in G361, a representative melanoma cell line/ reacted with autoantibodies in patient sera (PMID:20181627)
• eEF-2 is activated by both lithium and GSK-3, whereas, lithium treatment and inhibition of GSK-3 have opposing effects on eEF-2. (PMID:20708687)
• Training in the fasted state, compared with identical training with ample carbohydrate intake, facilitates post-exercise dephosphorylation of eEF2. (PMID:21132439)
• results suggest that eEF2 is an anti-apoptotic marker in lung adenocarcinoma (PMID:21554491)
• NH125 induces eEF2 phosphorylation (peEF2) through multiple pathways in cancer cells (PMID:22020937)
• Burn induces prolonged activation of eEF2K and eEF2 in pediatric patients. (PMID:22269896)
• PHD2 modulated eEF2 activity and protein translation under acute hypoxia. (PMID:22308030)
• A single amino acid substitution in eukaryotic elongation factor 2 co-segregates with the disease phenotype of spinocerebellar ataxia 26. (PMID:23001565)
• 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)
• nuclear localization of active eEF-2 depends upon its interaction with p53, as cells lacking p53 contain less active eEF-2 in the nuclear compartment (PMID:23542375)
• the direct interaction of AKT2 and EF2 was found to be dynamically regulated in embryonic rat cardiomyocytes (PMID:23823123)
• Thiopental inhibits global protein synthesis by repression of eukaryotic elongation factor 2 and protects from hypoxic neuronal cell death. (PMID:24167567)
• High serum eukaryotic elongation factor 2 level is associated with non-small cell lung cancer. (PMID:24377563)
• The expression levels of three putative HA-regulated proteins (TALDO, ANXA1 and EF2) in control, H2O2-, HA- and HA/H2O2-treated OA chondrocytes were verified by Western blotting and the results indeed support the notion that HA acts in anti-oxidation (PMID:24480285)
• Results indicated that the eEF2 gene is overexpressed in the majority of several types of cancers and plays an oncogenic role in cancer cell growth. (PMID:24589652)
• Data indicate that the accumulation of the cleaved C-terminal small fragment of eukaryotic elongation factor 2 (eEF2) in the nucleus, and C-terminal Src kinase (Csk) could enhance the proteolytic cleavage of eEF2. (PMID:24648518)
• These results suggest that binding of eEF2 to the ribosome alters its conformation, resulting in a weakened affinity of eIF5A and impairment of this interplay compromises cell growth due to translation elongation defects. (PMID:27115996)
• our study indicates that expression of eEF2 protein is a potential biomarker for evaluating prostate cancer (PMID:28913610)
• our findings provide new insights into the tumor suppressor role of miR-34a by dual-targeting of FOXM1/eEF2K signaling axis and suggest that miR-34a-based gene therapy may be a potential therapeutic strategy in triple-negative breast cancer (TNBC) (PMID:29748184)
• eEF2 may be activated in a positive feedback cycle through inactivation of eEF2K via the PI3K/Akt/mTOR pathway. (PMID:30060827)
• the MEK1/2-ERK1/2 pathway and the PKC pathway, but not the mTORC1-S6K1 pathway, are involved in mAChR-mediated eEF2 dephosphorylation. (PMID:31227218)
• miR-183-5p acts as a potential prognostic biomarker in gastric cancer and regulates cell functions by modulating EEF2 (PMID:31558304)
• The eEF2 kinase-induced STAT3 inactivation inhibits lung cancer cell proliferation by phosphorylation of PKM2. (PMID:32054489)
• miR-642a-5p partially mediates the effects of lipopolysaccharide on human pulmonary microvascular endothelial cells via eEF2. (PMID:32881411)
• Identification of the transcription factor Miz1 as an essential regulator of diphthamide biosynthesis using a CRISPR-mediated genome-wide screen. (PMID:33057331)
• De Novo variants in EEF2 cause a neurodevelopmental disorder with benign external hydrocephalus. (PMID:33355653)
• PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation. (PMID:33662272)
• Analysis of senescence-responsive stress fiber proteome reveals reorganization of stress fibers mediated by elongation factor eEF2 in HFF-1 cells. (PMID:34705524)
• Identification of a novel recurrent EEF2 gene amplification in familial prostate tumors. (PMID:36520140)
• eEF2 improves dense connective tissue repair and healing outcome by regulating cellular death, autophagy, apoptosis, proliferation and migration. (PMID:37084140)
• The FAM86 domain of FAM86A confers substrate specificity to promote EEF2-Lys525 methylation. (PMID:37209825)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef2l2	ENSDARG00000035256
mus_musculus	Eef2	ENSMUSG00000034994
rattus_norvegicus	Eef2	ENSRNOG00000020266
drosophila_melanogaster	eEF2	FBGN0000559
caenorhabditis_elegans	eef-2	WBGENE00001167

Paralogs (18): MTIF2 (ENSG00000085760), GTPBP1 (ENSG00000100226), EEF1A2 (ENSG00000101210), GSPT1 (ENSG00000103342), EFTUD2 (ENSG00000108883), HBS1L (ENSG00000112339), EIF2S3 (ENSG00000130741), EEFSEC (ENSG00000132394), EFL1 (ENSG00000140598), GUF1 (ENSG00000151806), EEF1A1 (ENSG00000156508), EIF5B (ENSG00000158417), GFM2 (ENSG00000164347), GFM1 (ENSG00000168827), GTPBP2 (ENSG00000172432), TUFM (ENSG00000178952), EIF2S3B (ENSG00000180574), GSPT2 (ENSG00000189369)

Protein

Protein identifiers

Elongation factor 2 — P13639 (reviewed: P13639)

All UniProt accessions (2): P13639, M0R0I6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome.

Subunit / interactions. Binds to 80S ribosomes. Actively translating ribosomes show mutually exclusive binding of eIF5a (EIF5A or EIF5A2) and EEF2/eEF2. Interacts with SERBP1; interaction sequesters EEF2/eEF2 at the A-site of the ribosome, thereby blocking the interaction sites of the mRNA-tRNA complex, promoting ribosome stabilization and hibernation. Interacts with HABP4; interaction takes place at the A-site of hibernating ribosomes and promotes ribosome stabilization. Component of the mRNA surveillance SURF complex, at least composed of ERF1, ERF3 (ERF3A or ERF3B), EEF2, UPF1/RENT1, SMG1, SMG8 and SMG9. Interacts with RBPMS2.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylation by EF-2 kinase completely inactivates EF-2; it requires prior phosphorylation by CDK2 at Ser-595 during mitotic prometaphase. Phosphorylation by CSK promotes SUMOylation, proteolytic cleavage, and nuclear translocation if the C-terminal fragment. Diphthamide is 2-[3-carboxyamido-3-(trimethyl-ammonio)propyl]histidine. (Microbial infection) Diphthamide can be ADP-ribosylated by diphtheria toxin and by Pseudomonas exotoxin A, thus arresting protein synthesis. ISGylated. Proteolytically processed at two sites following phosphorylation by CSK. SUMOylated following phosphorylation by CSK, promotes proteolytic cleavage.

Disease relevance. Spinocerebellar ataxia 26 (SCA26) [MIM:609306] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.

RefSeq proteins (1): NP_001952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000640	EFG_V-like	Domain
IPR000795	T_Tr_GTP-bd_dom	Domain
IPR004161	EFTu-like_2	Domain
IPR005225	Small_GTP-bd	Domain
IPR005517	Transl_elong_EFG/EF2_IV	Domain
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR014721	Ribsml_uS5_D2-typ_fold_subgr	Homologous_superfamily
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031157	G_TR_CS	Conserved_site
IPR035647	EFG_III/V	Homologous_superfamily
IPR041095	EFG_II	Domain

Pfam: PF00009, PF00679, PF03144, PF03764, PF14492

Enzyme classification (BRENDA):

• EC 3.6.5.3 — protein-synthesizing GTPase (BRENDA: 45 organisms, 101 substrates, 61 inhibitors, 66 Km, 48 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.0003–0.27	53
ATP	0.12–0.2	2

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (37 total): modified residue 22, binding site 3, cross-link 3, mutagenesis site 3, site 2, initiator methionine 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8XSX	ELECTRON MICROSCOPY	2.4
9P7D	ELECTRON MICROSCOPY	2.57
9P7E	ELECTRON MICROSCOPY	2.59
9P73	ELECTRON MICROSCOPY	2.66
9P9I	ELECTRON MICROSCOPY	2.77
9M0P	ELECTRON MICROSCOPY	2.78
9P7C	ELECTRON MICROSCOPY	2.78
9P7A	ELECTRON MICROSCOPY	2.81
9B0P	ELECTRON MICROSCOPY	2.82
9P9H	ELECTRON MICROSCOPY	2.84
9FQZ	ELECTRON MICROSCOPY	2.85
6Z6N	ELECTRON MICROSCOPY	2.9
9P78	ELECTRON MICROSCOPY	2.9
9I2E	ELECTRON MICROSCOPY	2.95
8UKB	ELECTRON MICROSCOPY	3.05
6Z6M	ELECTRON MICROSCOPY	3.1
9P79	ELECTRON MICROSCOPY	3.1
9P8C	ELECTRON MICROSCOPY	3.11
6D9J	ELECTRON MICROSCOPY	3.2
9B0Q	ELECTRON MICROSCOPY	3.2
8Y0X	ELECTRON MICROSCOPY	3.3
8Y0W	ELECTRON MICROSCOPY	3.4
9B0S	ELECTRON MICROSCOPY	3.8
4V6X	ELECTRON MICROSCOPY	5
9B0F
9B0G
9B0H
9B0J
9B0R
9B0W

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13639-F1	89.97	0.66

Functional residue map

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

Catalytic / active sites (2): 586–587 (cleavage); 605–606 (cleavage)

Ligand- & substrate-binding residues (3): 26–33; 158–161; 216–218

Post-translational modifications (25): 59, 152, 235, 239, 265, 272, 272, 275, 325, 373, 435, 439, 445, 502, 525, 572, 595, 619, 715, 715 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
595	strongly reduced phosphorylation at thr-57.
599	strongly reduced phosphorylation at thr-57.
715	confers resistance to diphtheria toxin.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-156902	Peptide chain elongation
R-HSA-5336415	Uptake and function of diphtheria toxin
R-HSA-5358493	Synthesis of diphthamide-EEF2
R-HSA-6798695	Neutrophil degranulation
R-HSA-8876725	Protein methylation

MSigDB gene sets: 370 (showing top): ATF_B, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_RESPONSE_TO_ESTRADIOL, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOCC_SECRETORY_GRANULE, MODULE_151, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GCM_NPM1

GO Biological Process (17): hematopoietic progenitor cell differentiation (GO:0002244), response to ischemia (GO:0002931), skeletal muscle contraction (GO:0003009), translational elongation (GO:0006414), response to xenobiotic stimulus (GO:0009410), glial cell proliferation (GO:0014009), response to estradiol (GO:0032355), response to endoplasmic reticulum stress (GO:0034976), skeletal muscle cell differentiation (GO:0035914), response to hydrogen peroxide (GO:0042542), response to ethanol (GO:0045471), positive regulation of translation (GO:0045727), response to folic acid (GO:0051593), translation at postsynapse (GO:0140242), cellular response to brain-derived neurotrophic factor stimulus (GO:1990416), positive regulation of cytoplasmic translation (GO:2000767), translation (GO:0006412)

GO Molecular Function (14): p53 binding (GO:0002039), RNA binding (GO:0003723), translation elongation factor activity (GO:0003746), GTPase activity (GO:0003924), GTP binding (GO:0005525), 5S rRNA binding (GO:0008097), protein kinase binding (GO:0019901), ribosome binding (GO:0043022), cadherin binding (GO:0045296), actin filament binding (GO:0051015), lncRNA binding (GO:0106222), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (15): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), plasma membrane (GO:0005886), membrane (GO:0016020), aggresome (GO:0016235), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), ficolin-1-rich granule lumen (GO:1904813), ribonucleoprotein complex (GO:1990904), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Eukaryotic Translation Elongation	1
Uptake and actions of bacterial toxins	1
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Innate Immune System	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell differentiation	2
translation	2
macromolecule biosynthetic process	2
response to oxygen-containing compound	2
translational elongation	2
synapse	2
hemopoiesis	1
response to stress	1
striated muscle contraction	1
musculoskeletal movement	1
response to chemical	1
cell population proliferation	1
gliogenesis	1
response to lipid	1
cellular response to stress	1
skeletal muscle tissue development	1
response to reactive oxygen species	1
response to alcohol	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
response to vitamin	1
response to nitrogen compound	1
postsynapse	1
translation at synapse	1
cellular response to nerve growth factor stimulus	1
cytoplasmic translation	1
positive regulation of translation	1
regulation of cytoplasmic translation	1
peptidyltransferase activity	1
translational initiation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
protein binding	1
nucleic acid binding	1
translation factor activity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1

Protein interactions and networks

STRING

7206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EEF2	EEF2K	O00418	986
EEF2	YTHDF1	Q9BYJ9	966
EEF2	DPH2	Q9BQC3	946
EEF2	DPH7	Q9BTV6	934
EEF2	DPH5	Q9H2P9	930
EEF2	DPH1	Q9BZG8	918
EEF2	EIF5A	P10159	918
EEF2	RPL8	P25120	913
EEF2	DPH3	Q96FX2	898
EEF2	RPS6	P08227	844
EEF2	EIF4A1	P04765	833
EEF2	EIF4A2	Q14240	819
EEF2	EIF5	P55010	815
EEF2	CALM1	P02593	811
EEF2	EIF4E	P06730	792
EEF2	CALML3	P27482	792

IntAct

260 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
MAPK14	RPS6KA4	psi-mi:“MI:0914”(association)	0.870
PPP2R1B	STRN	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
SMG1	TTI1	psi-mi:“MI:0914”(association)	0.600
EEF2	HTT	psi-mi:“MI:0915”(physical association)	0.560
DAPK1	SVIL	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
EEF2KMT	BCAT2	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
NME1	NME2P1	psi-mi:“MI:0914”(association)	0.530
HSD17B10	EEF2	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (730): EEF2 (Affinity Capture-MS), EEF2 (Biochemical Activity), EEF2 (Biochemical Activity), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-RNA), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS), EEF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A3B3IRV3, A0SXL6, A5DK38, A5PKR8, B6K286, O13914, O14179, P05197, P09445, P13188, P13639, P14325, P29691, P55823, P58252, P87313, P89886, Q07803, Q07953, Q09191, Q23716, Q25566, Q2KIE4, Q3SYU2, Q4G009, Q54Y20, Q554D9, Q5PPY1, Q5R8Z3, Q5ZI42, Q6BIJ0, Q6BPD3, Q6CA26, Q6CJ62, Q6DER1, Q6NRJ7, Q6P3J5, Q75AA8, Q75CZ5, Q7ZV34

Diamond homologs: A0B7D5, A0RW30, A0SXL6, A1RVX2, A3CXM8, A3DMV6, A3MSN3, A4FWF0, A4WMR8, A4YCV9, A5DI11, A5ULM6, A6UV44, A6VGV5, A7I4X4, A8ACA7, A9A9U4, A9B746, B0R8C8, B1L7Q0, B1YE08, B6YVG5, B8D6B2, B8GJK8, C3MQ53, C3MVH1, C3N5S0, C3NED6, C3NHB6, C4KHE9, C4YJQ8, C5A6N7, C6A4M0, C7NYH7, D3E3N9, O14460, O23755, O27131, O28385, O59521

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
EEF2K	down-regulates	EEF2	phosphorylation
DPH5	“down-regulates activity”	EEF2	methylation
EEF2	up-regulates	Translational_regulation
EEF2	up-regulates	Translational_elongation
EEF2	“up-regulates activity”	80S_cytosolic_ribosome	binding
CSK	“down-regulates quantity”	EEF2	phosphorylation
PPP2CA	up-regulates	EEF2	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 208 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
MAP kinase activation	6	11.9×	9e-04
DAP12 signaling	5	11.8×	2e-03
Aggrephagy	7	11.1×	6e-04
RHO GTPases activate IQGAPs	5	11.1×	3e-03
RAF activation	5	10.8×	3e-03
Interleukin-17 signaling	6	9.8×	2e-03
Negative regulation of the PI3K/AKT network	5	8.9×	4e-03
Selective autophagy	5	8.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	6	10.8×	4e-03
microtubule cytoskeleton organization	10	6.8×	2e-03
positive regulation of apoptotic process	13	4.2×	4e-03
intracellular signal transduction	16	3.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	248
Likely benign	181
Benign	71

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1047892	GRCh37/hg19 19p13.3(chr19:3976203-4345430)	Pathogenic
3361085	NM_001961.4(EEF2):c.328G>A (p.Asp110Asn)	Pathogenic
66077	NM_001961.4(EEF2):c.1787C>A (p.Pro596His)	Pathogenic
1315717	NM_001961.4(EEF2):c.433C>T (p.Gln145Ter)	Likely pathogenic
1696864	NM_001961.4(EEF2):c.2314G>A (p.Glu772Lys)	Likely pathogenic
3775634	NM_001961.4(EEF2):c.2008dup (p.Gln670fs)	Likely pathogenic
4246759	NM_001961.4(EEF2):c.1592A>C (p.Asp531Ala)	Likely pathogenic

SpliceAI

1946 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3976747:CCT:C	acceptor_loss	1.0000
19:3976748:C:CC	acceptor_gain	1.0000
19:3976748:CTGCA:C	acceptor_loss	1.0000
19:3977210:CTCA:C	donor_loss	1.0000
19:3977212:CA:C	donor_loss	1.0000
19:3977213:A:AC	donor_gain	1.0000
19:3977213:AC:A	donor_gain	1.0000
19:3977213:ACCA:A	donor_loss	1.0000
19:3977214:C:CT	donor_gain	1.0000
19:3977214:CC:C	donor_gain	1.0000
19:3977214:CCA:C	donor_gain	1.0000
19:3977214:CCAA:C	donor_gain	1.0000
19:3977343:GGACA:G	acceptor_gain	1.0000
19:3977344:GACA:G	acceptor_gain	1.0000
19:3977345:ACA:A	acceptor_gain	1.0000
19:3977346:CA:C	acceptor_gain	1.0000
19:3977346:CAC:C	acceptor_gain	1.0000
19:3977347:AC:A	acceptor_loss	1.0000
19:3977348:C:CC	acceptor_gain	1.0000
19:3977352:C:CT	acceptor_gain	1.0000
19:3977352:C:T	acceptor_gain	1.0000
19:3977353:A:T	acceptor_gain	1.0000
19:3977422:CCTCA:C	donor_loss	1.0000
19:3977423:CTCA:C	donor_loss	1.0000
19:3977424:TCAC:T	donor_loss	1.0000
19:3977426:ACCTG:A	donor_loss	1.0000
19:3977606:GCGCC:G	acceptor_gain	1.0000
19:3977607:CGCC:C	acceptor_gain	1.0000
19:3977607:CGCCC:C	acceptor_gain	1.0000
19:3977608:GCC:G	acceptor_gain	1.0000

AlphaMissense

5669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3976565:C:G	D856H	1.000
19:3976615:C:G	R839P	1.000
19:3976616:G:T	R839S	1.000
19:3976680:C:A	W817C	1.000
19:3976680:C:G	W817C	1.000
19:3976682:A:G	W817R	1.000
19:3976682:A:T	W817R	1.000
19:3976704:G:C	F809L	1.000
19:3976704:G:T	F809L	1.000
19:3976706:A:G	F809L	1.000
19:3976708:G:T	A808E	1.000
19:3976732:A:G	L800P	1.000
19:3977221:A:G	S793P	1.000
19:3977229:A:T	V790D	1.000
19:3977235:A:G	L788P	1.000
19:3977241:G:T	A786D	1.000
19:3977242:C:G	A786P	1.000
19:3977295:C:T	G768D	1.000
19:3977296:C:G	G768R	1.000
19:3977298:C:G	R767P	1.000
19:3977450:G:T	P743H	1.000
19:3977486:G:T	A731D	1.000
19:3977498:C:G	R727P	1.000
19:3977501:C:G	R726P	1.000
19:3977518:C:A	Q720H	1.000
19:3977518:C:G	Q720H	1.000
19:3977522:C:T	G719D	1.000
19:3977523:C:G	G719R	1.000
19:3977525:C:T	G718E	1.000
19:3977528:C:T	G717E	1.000

dbSNP variants (sampled 300 via entrez): RS1000079314 (19:3983654 G>A,C), RS1000478169 (19:3981303 G>A), RS1000492123 (19:3978292 A>C,G,T), RS1000527322 (19:3982172 G>A,C), RS1000542396 (19:3978465 A>T), RS1000661442 (19:3985269 G>A,C,T), RS1000924853 (19:3986681 A>C), RS1001197217 (19:3980639 T>C), RS1001215525 (19:3982006 G>A), RS1001266215 (19:3983536 C>A), RS1001339354 (19:3983966 G>A,T), RS1001483039 (19:3980415 T>C), RS1001605096 (19:3981240 G>A,C), RS1001911435 (19:3977673 G>A), RS1002737546 (19:3983782 T>C,G)

Disease associations

OMIM: gene MIM:130610 | disease phenotypes: MIM:609306, MIM:607346

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia type 26	Strong	Autosomal dominant
neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (4): obesity disorder (MONDO:0011122), spinocerebellar ataxia type 26 (MONDO:0012246), spinocerebellar ataxia type 19/22 (MONDO:0011819), neurodevelopmental disorder (MONDO:0700092)

Orphanet (4): Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Spinocerebellar ataxia type 26 (Orphanet:101112), Spinocerebellar ataxia type 19/22 (Orphanet:98772), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

20 total (21 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000639	Nystagmus
HP:0000641	Dysmetric saccades
HP:0001151	Impaired horizontal smooth pursuit
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001272	Cerebellar atrophy
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002073	Progressive cerebellar ataxia
HP:0002078	Truncal ataxia
HP:0002311	Incoordination
HP:0002380	Fasciculations
HP:0003470	Paralysis
HP:0003474	Somatic sensory dysfunction
HP:0003487	Babinski sign
HP:0003581	Adult onset
HP:0003677	Slowly progressive
HP:0007034	Generalized hyperreflexia
HP:0007240	Progressive gait ataxia
HP:0001513	Obesity

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C537198	Spinocerebellar ataxia 19 (supp.)
C542540	Spinocerebellar ataxia 22 (supp.)
C537203	Spinocerebellar ataxia 26 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795108 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Ribosomal factors

ChEMBL bioactivities

4 potent at pChembl≥5 of 6 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	IC50	60	nM	CHEMBL1683636
6.55	IC50	280	nM	CHEMBL1977874
5.39	Kd	4032	nM	CHEMBL3752910
5.39	ED50	4032	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 32 total; 1 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-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148289: Binding affinity to human EEF2 incubated for 45 mins by Kinobead based pull down assay	kd	4.0318	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression	5
sodium arsenite	decreases expression, increases activity, increases expression	3
Tobacco Smoke Pollution	increases expression, increases metabolic processing, affects expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
perfluorooctanoic acid	decreases expression	2
ochratoxin A	increases expression	2
bisphenol S	decreases expression, increases expression, affects cotreatment	2
Valproic Acid	affects expression, increases methylation	2
Metribolone	affects binding, increases reaction, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
methylparaben	increases expression	1
butylidenephthalide	increases expression	1
coumarin	affects phosphorylation	1
quinoline	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Coptidis rhizoma extract	increases phosphorylation, decreases activity	1
tanespimycin	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1228363	Binding	Inhibition of eEF2-mediated tRNA translocation assessed as inhibition of polyphenylalanine synthesis at 200 uM after 10 mins by scintillation counting	Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. — Nat Chem Biol

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0P39	5H7	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00076362	PHASE4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	PHASE4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	PHASE4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	PHASE4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	PHASE4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	PHASE4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	PHASE4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	PHASE4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	PHASE4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	PHASE4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	PHASE4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	PHASE4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	PHASE4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	PHASE4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	PHASE4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	PHASE4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	PHASE4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	PHASE4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	PHASE4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	PHASE4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	PHASE4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	PHASE4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	PHASE4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	PHASE4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	PHASE4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	PHASE4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	PHASE4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	PHASE4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	PHASE4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	PHASE4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	PHASE4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	PHASE4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	PHASE4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	PHASE4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	PHASE4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	PHASE4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)