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GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EEF1A1
eukaryotic translation elongation factor 1 alpha 1
Chromosome 6 · 6q13
NCBI Gene: 1915Ensembl: ENSG00000156508.21HGNC: HGNC:3189UniProt: P68104
559PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
tRNA bindingRNA bindingtranslation elongation factor activityGTPase activitymitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiencysevere acute respiratory syndromeAbnormal brain morphologybenign neoplasm of eye
✦AI Summary

EEF1A1 (eukaryotic translation elongation factor 1 alpha 1) is a multifunctional GTPase that catalyzes aminoacyl-tRNA delivery during protein synthesis elongation 1. Beyond its canonical translational role, EEF1A1 participates in protein ubiquitination, nuclear translocation, and quality control of stalled ribosomes 2. The protein's activity is dynamically regulated through post-translational modifications; METTL13-catalyzed lysine 55 dimethylation enhances EEF1A1 GTPase activity to increase protein synthesis 3, while K273 ubiquitination by FBXO32 similarly promotes translational output 4. Mechanistically, eEF1A1 works with elongation factors and ribosomal proteins to achieve higher decoding fidelity in eukaryotes compared to bacteria 1. During ribosome stalling, eEF1A1 undergoes RNF14/RNF25-dependent ubiquitination monitored by the collision sensor GCN1 5. EEF1A1 dysregulation is implicated in multiple cancers, including hepatocellular carcinoma 6 and pancreatic cancer, where FBXO32-eEF1A1 signaling drives metastasis through focal adhesion kinase activation 4. Additionally, eEF1A1 cooperates with translational regulators like RREB1 to selectively enhance mitochondrial protein translation in acute myeloid leukemia 7. Targeting the eEF1A1 axis shows therapeutic promise in cancer treatment.

Sources cited
1
EEF1A1 participates in aminoacyl-tRNA delivery and achieves higher decoding fidelity in eukaryotes through distinct kinetic and structural mechanisms compared to bacteria
PMID: 37020024
2
EEF1A1 participates in protein ubiquitination, nuclear translocation, and forms complexes regulating glycolytic reprogramming in macrophages
PMID: 39973763
3
METTL13-catalyzed dimethylation of eEF1A lysine 55 increases GTPase activity and protein synthesis to promote Ras-driven tumorigenesis
PMID: 30612740
4
FBXO32 promotes eEF1A1 ubiquitination at K273, enhancing its activity and selectively increasing ITGB5 translation to drive pancreatic cancer progression and metastasis
PMID: 38775804
5
EEF1A1 is ubiquitinated and degraded on stalled ribosomes through an E3 ligase network comprising RNF14 and RNF25, monitored by ribosome collision sensor GCN1
PMID: 36638793
6
EEF1A1 is significantly mutated in hepatocellular carcinoma cases
PMID: 28622513
7
EEF1A1 cooperates with translational regulator RREB1 to enhance selective translation of nuclear-encoded mitochondrial proteins in acute myeloid leukemia
PMID: 39357516
8
EEF1A1 is a secreted protein identified in cervical extracellular matrix associated with tumor microenvironment maintenance
PMID: 38748808
Disease Associationsⓘ20
mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiencyOpen Targets
0.54Moderate
severe acute respiratory syndromeOpen Targets
0.37Weak
Abnormal brain morphologyOpen Targets
0.33Weak
benign neoplasm of eyeOpen Targets
0.31Weak
genetic disorderOpen Targets
0.19Weak
skin cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Weak
skin neoplasmOpen Targets
0.10Suggestive
cancerOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
systemic lupus erythematosusOpen Targets
0.07Suggestive
diffuse large B-cell lymphomaOpen Targets
0.07Suggestive
infectionOpen Targets
0.07Suggestive
gastric cancerOpen Targets
0.07Suggestive
prostate cancerOpen Targets
0.07Suggestive
type 1 diabetes mellitusOpen Targets
0.05Suggestive
Parkinson diseaseOpen Targets
0.04Suggestive
skin diseaseOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RPL12Protein interaction100%RPS15AProtein interaction100%RPS9Protein interaction100%RPS23Protein interaction100%RPL13AProtein interaction100%RPL27Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Brain
53%
Lung
52%
Bone Marrow
50%
Liver
38%
Heart
21%
Gene Interaction Network
Click a node to explore
EEF1A1RPL12RPS15ARPS9RPS23RPL13ARPL27
PROTEIN STRUCTURE
Preparing viewer…
PDB3C5J · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.13Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.03 [0.01–0.13]
RankingsWhere EEF1A1 stands among ~20K protein-coding genes
  • #436of 20,598
    Most Researched559 · top 5%
  • #127of 17,882
    Most Constrained (LOEUF)0.13 · top 1%
Genes detectedEEF1A1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma.
PMID: 28622513
Cell · 2017
1.00
2
An E3 ligase network engages GCN1 to promote the degradation of translation factors on stalled ribosomes.
PMID: 36638793
Cell · 2023
0.90
3
Targeting TUBB2B inhibits triple-negative breast cancer growth and brain-metastatic colonization.
PMID: 39962586
J Exp Clin Cancer Res · 2025
0.86
4
CEP112 coordinates translational regulation of essential fertility genes during spermiogenesis through phase separation in humans and mice.
PMID: 39349455
Nat Commun · 2024
0.84
5
METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis.
PMID: 30612740
Cell · 2019
0.80