EEF1A1

Summary

EEF1A1 (eukaryotic translation elongation factor 1 alpha 1, HGNC:3189) is a protein-coding gene on chromosome 6q13, encoding Elongation factor 1-alpha 1 (P68104). Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas, and the other isoform (alpha 2) is expressed in brain, heart and skeletal muscle. This isoform is identified as an autoantigen in 66% of patients with Felty syndrome. This gene has been found to have multiple copies on many chromosomes, some of which, if not all, represent different pseudogenes.

Source: NCBI Gene 1915 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3189
Approved symbol	EEF1A1
Name	eukaryotic translation elongation factor 1 alpha 1
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	EE1A1, EF1A1, EF1alpha1
Ensembl gene	ENSG00000156508
Ensembl biotype	protein_coding
OMIM	130590
Entrez	1915

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 31 protein_coding, 8 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000309268, ENST00000316292, ENST00000331523, ENST00000356303, ENST00000423099, ENST00000455918, ENST00000488500, ENST00000490569, ENST00000491404, ENST00000495333, ENST00000610520, ENST00000615060, ENST00000676547, ENST00000676710, ENST00000677062, ENST00000677236, ENST00000678041, ENST00000678143, ENST00000678508, ENST00000678515, ENST00000678702, ENST00000678703, ENST00000679031, ENST00000850907, ENST00000850908, ENST00000850909, ENST00000875814, ENST00000875815, ENST00000875816, ENST00000875817, ENST00000933273, ENST00000933274, ENST00000933275, ENST00000933276, ENST00000933277, ENST00000933278, ENST00000933279, ENST00000933280, ENST00000967435, ENST00000967436

RefSeq mRNA: 1 — MANE Select: NM_001402 NM_001402

CCDS: CCDS4980

Canonical transcript exons

ENST00000309268 — 8 exons

Exon	Start	End
ENSE00001191875	73519883	73520056
ENSE00001202443	73518030	73518264
ENSE00001243576	73518354	73518610
ENSE00001830298	73515750	73517934
ENSE00003568244	73518698	73518848
ENSE00003675739	73519337	73519516
ENSE00003685376	73518932	73519228
ENSE00003746460	73521000	73521032

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 100.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.4878 / max 610.0781, expressed in 1821 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74376	30.1128	1813
74371	4.5930	1166
74379	1.9625	1124
74378	1.7053	1023
74380	1.4379	992
74382	0.9557	468
74383	0.9314	540
74373	0.4859	231
74381	0.4744	217
74372	0.3572	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	100.00	gold quality
embryo	UBERON:0000922	100.00	gold quality
ventricular zone	UBERON:0003053	100.00	gold quality
ganglionic eminence	UBERON:0004023	100.00	gold quality
cortical plate	UBERON:0005343	100.00	gold quality
endocervix	UBERON:0000458	99.99	gold quality
smooth muscle tissue	UBERON:0001135	99.99	gold quality
gall bladder	UBERON:0002110	99.99	gold quality
right ovary	UBERON:0002118	99.99	gold quality
left ovary	UBERON:0002119	99.99	gold quality
body of uterus	UBERON:0009853	99.99	gold quality
granulocyte	CL:0000094	99.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.98	gold quality
vermiform appendix	UBERON:0001154	99.98	gold quality
descending thoracic aorta	UBERON:0002345	99.98	gold quality
ectocervix	UBERON:0012249	99.98	gold quality
monocyte	CL:0000576	99.97	gold quality
leukocyte	CL:0000738	99.97	gold quality
rectum	UBERON:0001052	99.97	gold quality
right lobe of thyroid gland	UBERON:0001119	99.97	gold quality
left lobe of thyroid gland	UBERON:0001120	99.97	gold quality
mucosa of stomach	UBERON:0001199	99.97	gold quality
left adrenal gland	UBERON:0001234	99.97	gold quality
right uterine tube	UBERON:0001302	99.97	gold quality
left uterine tube	UBERON:0001303	99.97	gold quality
skin of abdomen	UBERON:0001416	99.97	gold quality
ascending aorta	UBERON:0001496	99.97	gold quality
thoracic aorta	UBERON:0001515	99.97	gold quality
right coronary artery	UBERON:0001625	99.97	gold quality
left coronary artery	UBERON:0001626	99.97	gold quality

Single-cell (SCXA)

Detected in 56 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	64943.77
E-HCAD-15	yes	27856.31
E-GEOD-81547	yes	23405.25
E-MTAB-6678	yes	19770.61
E-MTAB-10042	yes	11220.75
E-HCAD-9	yes	8864.11
E-MTAB-11268	yes	8306.51
E-MTAB-9543	yes	5187.26
E-MTAB-9221	yes	55.59
E-HCAD-35	yes	20.76
E-GEOD-137537	yes	6.47
E-HCAD-25	yes	4.78
E-CURD-79	no	33953.41
E-HCAD-4	no	29880.93
E-CURD-120	no	29148.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
ACTA1
GH1
MYH6

Upstream regulators (CollecTRI, top): GBX2, KLF9, SP1, TCF3, TP53, TP73

miRNA regulators (miRDB)

139 targeting EEF1A1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Eukaryotic elongation factor 1A (eEF1A) and tRNA are RanGTP-dependent binding partners of exportin-5 (Exp5). Exp5 stimulates nuclear export of eEF1A and tRNA. (PMID:12426393)
• The fragile X mental retardation protein FMRP binds elongation factor 1A mRNA and negatively regulates its translation in vivo. (PMID:12594214)
• TCTP preferentially stabilized the GDP form of eEF1A, and, furthermore, impaired the GDP exchange reaction promoted by eEF1Bbeta. (PMID:14623968)
• analysis of the relationships between EF-Ts and EF-Tu from both yeasts and humans through functional complementation and coexpression experiments (PMID:15695360)
• The potential roles of the PTI-1 protein in carcinogenesis and the origin of the PTI-1 gene in the human genome are discussed. (PMID:15716006)
• Our results indicate that neither EEF1A1 nor IMPG1 could be responsible for RP25 in the studied families due to absence of any pathogenic variants. (PMID:16354621)
• The cytotoxicity of G-rich GT oligomers was shown to be tightly related to their binding affinity for eEF1A protein. (PMID:16689924)
• potential tumor suppressor activity of CCS-3 may be mediated by its interaction with PLZF. (PMID:16828757)
• The interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity. (PMID:17332776)
• Endogenous HDM2- EF1alpha complex was detected in cancer cells overexpressing HDM2, suggesting a possible role of this interaction in HDM2-mediated oncogenesis. (PMID:17373842)
• identified the multifunctional eukaryotic translation elongation factor eEF1A1 as a novel interaction partner of PASKIN in the nuclei of testis germ cells and in the midpiece of sperm tails (PMID:17595531)
• The expression level of EEF1A1 correlates with cell growth but not apoptosis in hepatocellular carcinoma cell lines with different differentiation grades. (PMID:17825975)
• Up-regulation of muscle EEF1A1 relates to proteolysis rate, suggesting an involvement of this gene in muscle catabolic response in hypercatabolic traumatized patients. (PMID:17998013)
• both eEF1A and MYPT1 have roles in EGCG signaling for cancer prevention through 67LR (PMID:18079119)
• The ability of eEF1A1 rather than eEF1A2 to interact with calmodulin is predicted by MD analysis and showed experimentally. (PMID:18221514)
• a novel mechanism of regulation of both SK1 and SK2 that is mediated by their interaction with eEF1A. (PMID:18263879)
• These results indicate that the novel gene AngRem104 is involved in the in vivo regulation of GR expression and the activation of NF-kappaB through interaction with GR-EF in human MCs. (PMID:18331827)
• It was demonstrated that the N protein of SARS-CoV induces aggregation of EF1, inhibiting protein translation and cytokinesis by blocking F-actin bundling. (PMID:18448518)
• BPOZ-2 promoted eEF1A1 ubiquitylation and degradation, suggesting that eEF1A1 is a substrate of BPOZ-2. (PMID:18459963)
• eEF1A1 is a novel endothelial nitric oxide synthase 3’-untranslated region binding protein that plays a critical role in mediating tumor necrosis factor (TNF)-alpha-induced decrease in eNOS mRNA stability. (PMID:18688046)
• The cell death was associated with downregulation of eukaryotic translation elongation factor-1 alpha 1 (eEF1A1/EF-1alpha) expression in conjunction with accumulation of its mRNA in processing bodies (P bodies). (PMID:18820646)
• PTI-1 presence parallels Mycoplasma infection suggesting that PTI-1 might not necessarily play a major role in the onset of prostate tumorigenesis. (PMID:18853312)
• EF1A1 regulation of OPN mRNA stability is actin dependent. EF1A1 is a regulatory factor in OPN expression in cancer. (PMID:19026636)
• This finding reveals a novel contribution of the SAM-EF1A1 interaction as a potentially important GAP-independent modulation of cell migration by DLC1. (PMID:19158340)
• confirm the interactions of eEF1A1, p54(nrb), hnRNP-L, GAPDH and ASF/SF2 with the right terminal stem-loop domain of HDV genomic RNA in vitro (PMID:19464723)
• The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of ZBTB7A protein appears to enhance ZBTB7A protein mediated transcriptional repression. (PMID:19471103)
• The decapeptide 50GKGSFKYAWV59 of eukaryotic elongation factor 1A is efficiently modified by Legionella pneumophila glucosyltransferase Lgt1. (PMID:19478083)
• Cathepsin D and eEF1 are promising markers for the detection of cellular senescence induced by a variety of treatments. (PMID:19487283)
• These findings suggest that the interaction between LRRK2 and EF1A may reciprocally modulate their physiological function. (PMID:19559761)
• created and validated comparative three-dimensional (3-D) models of eEF1A1 and eEF1A2 on the basis of the crystal structure of homologous eEF1A from yeast (PMID:19636410)
• The structures of LppGT/LplGT (lpg1368 and lpl1319) reveal three domains and suggest that a positively charged EF1A loop binds to a negatively charged groove on the LpGT structure, and that two asparagine residues are essential for catalysis. (PMID:20030628)
• Proteomics was used to study colonic epithelial aging, for differential proteins in the human normal colonic epithelial tissues from young and old people. Rack1, EF-Tu and Rhodanese, three validated differential proteins, were further investigated. (PMID:20099848)
• These findings provide evidence that elongation factor-1 alpha correlates closely with the survival of patients with prostate cancer and may be a novel prognostic factor. (PMID:20545466)
• Data show that EF1alpha, RPL13a and YWHAZ are suitable genes for the RT-qPCR analysis and comparison of several sources of human MSC during in vitro characterization and differentiation as well as in an ex vivo animal model of global cerebral ischemia. (PMID:20716364)
• Phosphorylation of eEF1A1 by TbetaR-I is a novel regulatory mechanism that provides a direct link to regulation of protein synthesis by TGF-beta, as an important component in the TGF-beta-dependent regulation of protein synthesis and cell proliferation (PMID:20832312)
• study defines the mechanism regulating eEF1A-mediated SK1 activation, and also establishes SK1 as being integral for PTI-1-induced oncogenesis (PMID:20838377)
• A co-localization of SORBS2 and eEF1A was evidenced at level of plasma membrane, thus suggesting the involvement of eEF1A1 in novel key signal transduction complexes. (PMID:21689717)
• Human papillomavirus type 38 E7 protein promotes keratinocyte proliferation by negatively regulating actin cytoskeleton fiber formation through the CK2-MEK-ERK-Rho pathway and by inhibiting eEF1A and its effects on actin cytoskeleton remodeling. (PMID:21697493)
• An immunoreactive protein detected in sera from 21 of 40 infiltrating ductal breast carcinoma patients was isolated and subsequently identified as elongation factor-Tu. (PMID:21704614)
• Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable (PMID:22095224)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eef1a1a	ENSDARG00000039502
danio_rerio	eef1a1b	ENSDARG00000069951
drosophila_melanogaster	mEFTu2	FBGN0033184
drosophila_melanogaster	eIF2gamma	FBGN0263740
caenorhabditis_elegans	tufm-2	WBGENE00007001
caenorhabditis_elegans	eif-2gamma	WBGENE00021466

Paralogs (18): MTIF2 (ENSG00000085760), GTPBP1 (ENSG00000100226), EEF1A2 (ENSG00000101210), GSPT1 (ENSG00000103342), EFTUD2 (ENSG00000108883), HBS1L (ENSG00000112339), EIF2S3 (ENSG00000130741), EEFSEC (ENSG00000132394), EFL1 (ENSG00000140598), GUF1 (ENSG00000151806), EIF5B (ENSG00000158417), GFM2 (ENSG00000164347), EEF2 (ENSG00000167658), GFM1 (ENSG00000168827), GTPBP2 (ENSG00000172432), TUFM (ENSG00000178952), EIF2S3B (ENSG00000180574), GSPT2 (ENSG00000189369)

Protein

Protein identifiers

Elongation factor 1-alpha 1 — P68104 (reviewed: P68104)

Alternative names: Elongation factor Tu, Eukaryotic elongation factor 1 A-1, Leukocyte receptor cluster member 7

All UniProt accessions (9): P68104, A0A087WV01, A0A087WVQ9, A0A7I2V3H3, A0A7I2V5N4, A0A7I2V659, A6PW80, Q5JR01, Q6IPS9

UniProt curated annotations — full annotation on UniProt →

Function. Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome. The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation. Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1. Also plays a role in cytoskeleton organization by promoting actin bundling. (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection.

Subunit / interactions. Found in a nuclear export complex with XPO5, EEF1A1, Ran and aminoacylated tRNA. Interacts with PARP1. Interacts with KARS1. May interact with ERGIC2. Interacts with IFIT1 (via TPR repeats 4-7). Interacts with DLC1, facilitating distribution to the membrane periphery and ruffles upon growth factor stimulation. Interacts with ZPR1; the interaction occurs in a epidermal growth factor (EGF)-dependent manner. Interacts with PPP1R16B. Interacts with SPHK1 and SPHK2; both interactions increase SPHK1 and SPHK2 kinase activity. Interacts with guanyl-nucleotide exchange factor EEF1B2. Interacts (via middle-region) with HTATIP2 (via N-terminus); the interaction is direct and competes with EEF1A1 binding to guanyl-nucleotide exchange factor EEF1B2, thereby inhibiting GDP for GTP exchange and reactivation of EEF1A1. Interacts with tRNA. Interacts with CEP112.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Cell membrane.

Post-translational modifications. ISGylated. Phosphorylated by TXK. Phosphorylation by PASK increases translation efficiency. Phosphorylated by ROCK2. Phosphorylation by TGFBR1 inhibits translation elongation. Trimethylated at Lys-79 by EEF1AKMT1. Methylated at Lys-165 by EEF1AKMT3, methylation by EEF1AKMT3 is dynamic as well as inducible by stress conditions, such as ER-stress, and plays a regulatory role on mRNA translation. Trimethylated at Lys-318 by EEF1AKMT2. Mono-, di-, and trimethylated at Lys-36 by EEF1AKMT4; trimethylated form is predominant. Methylation by EEF1AKMT4 contributes to the fine-tuning of translation rates for a subset of tRNAs. Trimethylated at Gly-2 by METTL13. Mono- and dimethylated at Lys-55 by METTL13; dimethylated form is predominant. Ubiquitinated at Lys-385 by RNF14 in response to ribosome collisions (ribosome stalling), leading to its degradation by the proteasome and rescue of stalled ribosomes.

Activity regulation. Inhibited by plitidepsin, a chemical compound extracted from the ascidian Aplidium albicans. Specifically inhibited by didemnin B, a natural product that triggers ribosome stalling by preventing aminoacyl-tRNA (aa-tRNA) release from EEF1A1 on the ribosome. Specifically inhibited by ternatin-4, a small-molecule inhibitor that triggers ribosome stalling by traping EEF1A1 on the ribosome and preventing aminoacyl-tRNA (aa-tRNA) accommodation. Ribosome stalling by ternatin-4 causes ubiquitination and degradation of EEF1A1. Specifically inhibited by ternatin SR-A3, which differs from ternatin-4 by the addition of a single oxygen atom into the side chain of N-Me-Leu. Inhibition by ternatin-4 can be reversed, while it is not the case for didemnin B.

Induction. By homocysteine (HC), may mediate accelerated synthesis of free thiol-containing proteins in response to HC-induced oxidative stress.

Similarity. Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.

RefSeq proteins (1): NP_001393* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000795	T_Tr_GTP-bd_dom	Domain
IPR004161	EFTu-like_2	Domain
IPR004539	Transl_elong_EF1A_euk/arc	Family
IPR009000	Transl_B-barrel_sf	Homologous_superfamily
IPR009001	Transl_elong_EF1A/Init_IF2_C	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031157	G_TR_CS	Conserved_site
IPR050100	TRAFAC_GTPase_members	Family
IPR054696	GTP-eEF1A_C	Domain

Pfam: PF00009, PF03144, PF22594

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (43 total): modified residue 20, mutagenesis site 9, region of interest 5, binding site 3, sequence conflict 2, initiator methionine 1, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3C5J	X-RAY DIFFRACTION	1.8
9P8B	ELECTRON MICROSCOPY	2.48
8G60	ELECTRON MICROSCOPY	2.54
9P7O	ELECTRON MICROSCOPY	2.65
9PA7	ELECTRON MICROSCOPY	2.67
8G6J	ELECTRON MICROSCOPY	2.8
9P7K	ELECTRON MICROSCOPY	2.8
9P76	ELECTRON MICROSCOPY	2.83
9P7N	ELECTRON MICROSCOPY	2.83
9P7L	ELECTRON MICROSCOPY	2.92
6ZMO	ELECTRON MICROSCOPY	3.1
9P7H	ELECTRON MICROSCOPY	3.68
9P7I	ELECTRON MICROSCOPY	3.69
9AZC
9AZS
9B0N
9B0O

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P68104-F1	88.06	0.57

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 (3): 194–196; 14–21; 153–156

Post-translational modifications (21): 2, 36, 36, 36, 55, 79, 165, 165, 165, 165, 172, 273, 300, 301, 318, 374, 392, 392, 432, 439 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
36	no effect on methylation by eef1akmt2. abolishes eef1akmt4-mediated methylation.
55	no effect on methylation by eef1akmt2. abolishes methylation by mettl13.
79	no effect on methylation by eef1akmt2.
165	abolishes methylation by eef1akmt3.
165	no effect on methylation by eef1akmt2.
318	abolishes methylation by eef1akmt2.
385	impaired ubiquitination in response to ribosome stalling caused by ternatin-4.
399	resistant to inhibition by plitidepsin and ternatin-4. no effect on sars-cov-2 proteins translation.
432	abolishes phosphorylation by pask.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-156902	Peptide chain elongation
R-HSA-3371511	HSF1 activation
R-HSA-6798695	Neutrophil degranulation
R-HSA-8876725	Protein methylation
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9735869	SARS-CoV-1 modulates host translation machinery

MSigDB gene sets: 327 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, FXR_IR1_Q6, AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_151, GNF2_TPT1, GCANCTGNY_MYOD_Q6, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MATTIOLI_MGUS_VS_PCL, MODULE_150, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (5): translation (GO:0006412), translational elongation (GO:0006414), host-mediated activation of viral genome replication (GO:0044829), cellular response to epidermal growth factor stimulus (GO:0071364), regulation of chaperone-mediated autophagy (GO:1904714)

GO Molecular Function (12): tRNA binding (GO:0000049), RNA binding (GO:0003723), translation elongation factor activity (GO:0003746), GTPase activity (GO:0003924), GTP binding (GO:0005525), kinase activator activity (GO:0019209), kinase binding (GO:0019900), protein kinase binding (GO:0019901), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (17): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), ribosome (GO:0005840), eukaryotic translation elongation factor 1 complex (GO:0005853), plasma membrane (GO:0005886), membrane (GO:0016020), cytosolic ribosome (GO:0022626), cortical actin cytoskeleton (GO:0030864), ruffle membrane (GO:0032587), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), cytoplasmic side of lysosomal membrane (GO:0098574), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Translation	1
Eukaryotic Translation Elongation	1
Cellular response to heat stress	1
Innate Immune System	1
Post-translational protein modification	1
Autophagy	1
SARS-CoV-1-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translational elongation	2
macromolecule biosynthetic process	2
binding	2
intracellular membraneless organelle	2
cytoplasm	2
peptidyltransferase activity	1
translational initiation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
host-mediated activation of viral process	1
host-mediated perturbation of viral genome replication	1
response to epidermal growth factor	1
cellular response to growth factor stimulus	1
regulation of autophagy	1
regulation of protein catabolic process	1
chaperone-mediated autophagy	1
RNA binding	1
nucleic acid binding	1
translation factor activity	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme activator activity	1
kinase activity	1
kinase regulator activity	1
enzyme binding	1
kinase binding	1
molecular_function	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
protein-containing complex	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

372 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
EEF1G	EEF1B2	psi-mi:“MI:0914”(association)	0.890
MAPK14	RPS6KA4	psi-mi:“MI:0914”(association)	0.870
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
EEF1A1	TTLL12	psi-mi:“MI:0915”(physical association)	0.740
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
SUN2	LMNA	psi-mi:“MI:0914”(association)	0.720
MDM2	EEF1A1	psi-mi:“MI:0915”(physical association)	0.710
EEF1A1	MDM2	psi-mi:“MI:0915”(physical association)	0.710
ZBTB16	EEF1A1	psi-mi:“MI:0915”(physical association)	0.590
ZBTB16	EEF1A1	psi-mi:“MI:0407”(direct interaction)	0.590
EEF1A1	PCNA	psi-mi:“MI:0915”(physical association)	0.570
EEF1A1	BOD1	psi-mi:“MI:0915”(physical association)	0.560
EEF1A1	GADD45G	psi-mi:“MI:0915”(physical association)	0.550
EEF1A1	NLGN3	psi-mi:“MI:0915”(physical association)	0.540
EEF1A1	NLGN3	psi-mi:“MI:0403”(colocalization)	0.540
SPHK1	EEF1A1	psi-mi:“MI:0407”(direct interaction)	0.540
EEF1A1	SPHK1	psi-mi:“MI:0915”(physical association)	0.540
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530

BioGRID (1083): EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-RNA), EEF1A1 (Affinity Capture-RNA), EEF1A1 (Two-hybrid), EEF1A1 (Affinity Capture-Western), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), EEF1A1 (Reconstituted Complex), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS), EEF1A1 (Affinity Capture-MS)

ESM2 similar proteins: A2Q0Z0, A5DPE3, O42820, P02993, P02994, P05303, P06805, P08736, P0CN30, P0CN31, P0CT53, P0CT54, P0CT55, P10126, P13549, P14864, P14865, P17507, P17508, P19039, P28295, P29520, P34825, P41745, P41752, P53013, P62629, P62630, P62631, P62632, P68103, P68104, P68105, P86934, P86939, Q00251, Q01520, Q01765, Q05639, Q2HJN4

Diamond homologs: A0B7D6, A0RUM4, A1RRJ3, A1RXW9, A2BN41, A2Q0Z0, A2STF0, A3CTG3, A3DMQ1, A3MV69, A4FWE9, A4WKK8, A4YCR6, A5ULM5, A6UQ14, A6UV43, A6VGV6, A7I656, A8ABM5, A9A9U3, B0R8C3, B6YVG2, B8GIQ3, C5A5P4, C6A4R7, O27132, O29325, O59153, O64937, O93729, P02993, P05303, P07810, P08736, P0CT31, P0CT32, P10126, P13549, P16018, P17196

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
TGFBR1	down-regulates	EEF1A1	phosphorylation
EEF1A1	“form complex”	mTORC2	binding
PASK	unknown	EEF1A1	phosphorylation
Ternatin	“down-regulates activity”	EEF1A1	“chemical inhibition”
“EEF1B complex”	“up-regulates activity”	EEF1A1	“guanine nucleotide exchange factor”
EEF1A1	up-regulates	Translational_elongation
EEF1A1	up-regulates	Lys-tRNA(Lys)	relocalization
EEF1A1	up-regulates	Ala-tRNA(Ala)	relocalization
EEF1A1	up-regulates	Met-tRNA(Met)	relocalization
EEF1A1	up-regulates	Arg-tRNA(Arg)	relocalization
EEF1A1	up-regulates	Asn-tRNA(Asn)	relocalization
EEF1A1	up-regulates	Asp-tRNA(Asp)	relocalization
EEF1A1	up-regulates	Cys-tRNA(Cys)	relocalization
EEF1A1	up-regulates	Glu-tRNA(Glu)	relocalization
EEF1A1	up-regulates	Gln-tRNA(Gln)	relocalization
EEF1A1	up-regulates	His-tRNA(His)	relocalization
EEF1A1	up-regulates	Ile-tRNA(Ile)	relocalization
EEF1A1	up-regulates	Leu-tRNA(Leu)	relocalization
EEF1A1	up-regulates	Pro-tRNA(Pro)	relocalization
EEF1A1	up-regulates	Ser-tRNA(Ser)	relocalization
EEF1A1	up-regulates	Thr-tRNA(Thr)	relocalization
EEF1A1	up-regulates	Trp-tRNA(Trp)	relocalization
EEF1A1	up-regulates	Tyr-tRNA(Tyr)	relocalization
EEF1A1	up-regulates	Val-tRNA(Val)	relocalization
EEF1A1	up-regulates	Phe-tRNA(Phe)	relocalization
EEF1A1	up-regulates	Gly-tRNA(Gly)	relocalization
EEF1A1	“form complex”	EEF1A:GTP:aa-tRNA	binding
EEF1A1	“up-regulates activity”	SP1	binding
USP11	“up-regulates activity”	EEF1A1	deubiquitination
PRKCB	“up-regulates activity”	EEF1A1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 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
Signaling by ALK fusions and activated point mutants	7	7.6×	1e-02
Cellular responses to stress	15	4.0×	3e-03
Cellular responses to stimuli	16	3.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	12.4×	6e-03
mitophagy	6	11.0×	8e-03
G1/S transition of mitotic cell cycle	7	8.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1219 predictions. Top by Δscore:

Variant	Effect	Δscore
6:73492228:TTGCA:T	acceptor_loss	1.0000
6:73492229:TGCA:T	acceptor_loss	1.0000
6:73492230:GCAG:G	acceptor_loss	1.0000
6:73492231:CAG:C	acceptor_gain	1.0000
6:73492232:A:AG	acceptor_gain	1.0000
6:73492232:AGA:A	acceptor_gain	1.0000
6:73492233:G:GG	acceptor_gain	1.0000
6:73492233:GA:G	acceptor_gain	1.0000
6:73492233:GAG:G	acceptor_gain	1.0000
6:73492233:GAGCT:G	acceptor_gain	1.0000
6:73492306:G:GT	donor_gain	1.0000
6:73492348:AGAAG:A	donor_loss	1.0000
6:73492349:GAAGG:G	donor_loss	1.0000
6:73492350:A:T	donor_gain	1.0000
6:73492350:AAG:A	donor_loss	1.0000
6:73492351:AGG:A	donor_loss	1.0000
6:73492352:GGT:G	donor_loss	1.0000
6:73492353:GTAG:G	donor_loss	1.0000
6:73492354:T:G	donor_loss	1.0000
6:73497893:GACG:G	donor_gain	1.0000
6:73500730:T:G	donor_gain	1.0000
6:73517931:CGAC:C	acceptor_gain	1.0000
6:73517934:CCTAT:C	acceptor_loss	1.0000
6:73517935:C:CC	acceptor_gain	1.0000
6:73517935:CT:C	acceptor_loss	1.0000
6:73518024:CCTTA:C	donor_loss	1.0000
6:73518025:CTTAC:C	donor_loss	1.0000
6:73518026:TTACC:T	donor_loss	1.0000
6:73518027:TACCC:T	donor_loss	1.0000
6:73518028:A:AC	donor_gain	1.0000

AlphaMissense

3046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:73517886:A:T	I438N	1.000
6:73517889:A:T	V437D	1.000
6:73517892:C:A	G436V	1.000
6:73517892:C:T	G436D	1.000
6:73517893:C:A	G436C	1.000
6:73517893:C:G	G436R	1.000
6:73517893:C:T	G436S	1.000
6:73517895:A:T	V435E	1.000
6:73517898:G:T	A434E	1.000
6:73517899:C:G	A434P	1.000
6:73517901:A:T	V433D	1.000
6:73517904:G:A	T432I	1.000
6:73517910:C:A	R430I	1.000
6:73517916:T:A	D428V	1.000
6:73517916:T:C	D428G	1.000
6:73517916:T:G	D428A	1.000
6:73517917:C:A	D428Y	1.000
6:73517917:C:G	D428H	1.000
6:73517919:C:G	R427P	1.000
6:73517919:C:T	R427H	1.000
6:73517920:G:T	R427S	1.000
6:73517922:A:T	V426D	1.000
6:73517925:G:T	A425D	1.000
6:73517927:A:C	F424L	1.000
6:73517927:A:T	F424L	1.000
6:73517928:A:G	F424S	1.000
6:73517929:A:G	F424L	1.000
6:73517931:C:G	R423P	1.000
6:73517932:G:T	R423S	1.000
6:73517934:C:A	G422V	1.000

dbSNP variants (sampled 300 via entrez): RS1000235376 (6:73520422 G>A), RS1000315082 (6:73517341 T>C), RS1000407491 (6:73521641 C>G,T), RS1000790827 (6:73517217 A>G), RS1001396441 (6:73518540 A>G), RS1001666460 (6:73520568 C>G,T), RS1001721689 (6:73518857 C>A,G), RS1002008690 (6:73517436 A>G), RS1002216114 (6:73515300 C>T), RS1002669357 (6:73521419 C>A,G,T), RS1002784202 (6:73521268 C>A,T), RS1003150641 (6:73516509 T>C), RS1003276650 (6:73520583 G>C), RS1003575364 (6:73515484 C>T), RS1003738151 (6:73520702 C>T)

Disease associations

OMIM: gene MIM:130590 | disease phenotypes: MIM:614702, MIM:604369

GenCC curated gene-disease

Mondo (2): mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (MONDO:0013865), Salla disease (MONDO:0011449)

Orphanet (3): Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (Orphanet:314637), Salla disease (Orphanet:309334), Free sialic acid storage disease (Orphanet:834)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795120 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.43	Kd	3.74	nM	CHEMBL1802814
8.09	Kd	8.15	nM	CHEMBL1802815
7.24	Kd	57.2	nM	CHEMBL1802973

PubChem BioAssay actives

3 with measured affinity, of 28 total; 3 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
N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-4-[3-[(1R)-1-cyclohexylethyl]-2-(4-methoxyanilino)-8-oxopyrano[3,2-f]benzimidazol-6-yl]benzamide	606734: Binding affinity to eEF1A1 expressed in human MDA-MB-231 cells using 1 uM biotinylated compound immobilized on streptavidin sensor chip by surface plasmon resonance method	kd	0.0037	uM
N-[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-4-[3-benzyl-2-(2-methylpropylamino)-8-oxopyrano[3,2-f]benzimidazol-6-yl]benzamide	606734: Binding affinity to eEF1A1 expressed in human MDA-MB-231 cells using 1 uM biotinylated compound immobilized on streptavidin sensor chip by surface plasmon resonance method	kd	0.0081	uM
N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-4-[7-[[(1R)-1-cyclohexylethyl]amino]-6-nitro-4-oxochromen-2-yl]benzamide	606734: Binding affinity to eEF1A1 expressed in human MDA-MB-231 cells using 1 uM biotinylated compound immobilized on streptavidin sensor chip by surface plasmon resonance method	kd	0.0572	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, decreases expression, increases expression	6
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression, increases expression	4
sodium arsenite	decreases expression, increases expression, affects cotreatment	3
Benzo(a)pyrene	increases methylation, decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
Arsenic Trioxide	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, increases methylation	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
uranyl acetate	affects expression	1
sodium arsenate	increases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
trichostatin A	decreases expression	1
tetrahydropalmatine	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, increases expression	1
butylidenephthalide	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cadmium acetate	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
triphenyltin	decreases expression	1
phenanthrene	decreases expression	1
perfluorodecanoic acid	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1228364	Binding	Inhibition of eEF1A-mediated tRNA binding to ternary complex at 200 uM after 10 mins by filtration binding assay	Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. — Nat Chem Biol

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1E8	SEES3-1V human EEF1A1, clone1	Embryonic stem cell	Male
CVCL_A1E9	SEES3-1V human EEF1A1, clone2	Embryonic stem cell	Male
CVCL_A1F0	SEES3-1V human EEF1A1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project