# EEF1A1

## Overview
EEF1A1 is a gene that encodes the protein eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), which is essential for protein synthesis in eukaryotic cells. This protein is primarily involved in the elongation phase of translation, facilitating the delivery of aminoacyl-tRNAs to the ribosome. Beyond its central role in protein synthesis, EEF1A1 participates in a variety of other cellular processes, including cytoskeletal modulation, chaperone activities, and nuclear export of specific proteins. The protein structure of EEF1A1 is characterized by three domains, each contributing to its complex function and interaction with other cellular components. EEF1A1's involvement in multiple cellular pathways underscores its importance in maintaining cellular function and responding to environmental stresses (Mills2021On; Abbas2015The).

## Structure
The molecular structure of the human EEF1A1 protein is complex, comprising three distinct domains. Domain I, which spans residues 4-234, is crucial for GDP/GTP binding and features a Rossmann-fold topology, characterized by a β-sheet flanked by α-helices (Soares2009Structural; Mills2021On). Domain II, described as a β-barrel formed by several β-strands, ranges from residues 241-328, while Domain III, also a β-barrel structure, includes residues 337-462/463 (Mills2021On; Kanibolotsky2008Multiple).

The protein exhibits flexibility between its domains, facilitated by intrinsically disordered regions (IDRs), which allow EEF1A1 to adopt different conformations crucial for its function (Mills2021On). This flexibility is significant for the protein's ability to modulate cellular responses to environmental changes. EEF1A1 also participates in various non-canonical cellular functions, which depend on specific post-translational modifications (PTMs). One notable PTM is the attachment of phosphatidylethanolamine (PE) to glutamate residues, important for membrane association (Mills2021On).

The quaternary structure of EEF1A1 is not explicitly detailed in the provided contexts, suggesting a lack of clear information regarding the assembly of multiple protein subunits. However, the interaction between its domains suggests a complex folding pattern that facilitates its functional transitions (Kanibolotsky2008Multiple).

## Function
EEF1A1, or eukaryotic translation elongation factor 1 alpha 1, is a protein that plays a pivotal role in the elongation phase of protein synthesis in eukaryotic cells. It is responsible for the delivery of aminoacyl-tRNAs to the ribosome's A site in a GTP-dependent manner, a critical step in the translation of mRNA into polypeptides (Mills2021On). Beyond its canonical role in protein synthesis, EEF1A1 is involved in various cellular processes, including the modulation of the cytoskeleton, chaperone-like activities, and the nuclear export of specific proteins such as the VHL tumor suppressor and poly(A)-binding protein (PABP1) (Abbas2015The).

EEF1A1 also exhibits significant roles in cellular responses to environmental stress, particularly in the heat shock response (HSR). During HSR, it is involved in the transcription activation of heat shock protein 70 (HSP70) by recruiting the heat shock factor 1 (HSF1) to its promoter, enhancing mRNA stability and facilitating its transport from the nucleus to active ribosomes (Vera2014The). This coordination ensures a rapid and robust production of HSP70, crucial for cell survival under stress conditions.

Additionally, EEF1A1 undergoes numerous post-translational modifications, which add to the complexity of its function and regulation in cellular processes. These modifications can affect the protein's interaction with other molecular partners and influence its function in processes such as signal transduction and cytoskeletal organization (Mills2021On).

## Clinical Significance
EEF1A1 has been implicated in various cancers, where its expression levels are often altered. In colon adenocarcinoma, high expression of EEF1A1 is associated with favorable overall survival and disease-free survival, suggesting its potential as a prognostic biomarker (Joung2019Expression). Conversely, EEF1A1 generally shows reduced expression in several other cancers such as breast, lung, gastric, kidney, and head and neck cancers, with its expression levels inversely correlating with the proto-oncogenic isoform EEF1A2, which is linked to tumor progression (Hassan2018The). This differential expression indicates that EEF1A1 might play varying roles in cancer progression and patient outcomes depending on the cancer type and stage.

Furthermore, alterations in EEF1A1 expression or function can lead to significant biological effects, impacting oncogenesis and apoptosis. Overexpression of EEF1A1 is linked to enhanced cell proliferation and reduced apoptosis, critical factors in tumor development and progression (Abbas2015The). Additionally, specific mutations or alterations in EEF1A1's normal interactions have not been detailed, but its involvement in various cellular processes suggests a broader role in oncogenesis and potentially other diseases (Joung2019Expression).

## Interactions
EEF1A1 interacts with a variety of proteins and nucleic acids, reflecting its multifunctional role in cellular processes beyond its primary function in protein synthesis. It has been identified as a binding partner for the eEF1Ba protein, with a highly conserved binding site across different species, although interactions may vary by species or experimental conditions (Soares2009Structural). Additionally, EEF1A1 has been shown to interact with proteins involved in disease processes, such as SAMHD1, which is linked to Aicardi-Goutières syndrome and HIV-1 restriction. This interaction is mediated through the HD domain of SAMHD1 and may involve targeting SAMHD1 for proteasomal degradation (Morrissey2015The).

EEF1A1 also interacts with proteins containing expanded polyalanine tracts, which are implicated in various polyalanine expansion diseases. This interaction is mediated by domain III of EEF1A1 and is crucial for the nuclear export of these proteins (Li2017Expanded). Furthermore, EEF1A1 forms complexes with Sgt1, a co-chaperon protein involved in antiviral defense, where the interaction involves the D2 and D3 domains of EEF1A1 and the TPR domain of Sgt1 (Novosylna2015Translation). These interactions highlight EEF1A1's role in cellular defense mechanisms and its potential as a therapeutic target in disease treatment and prevention.


## References


[1. (Soares2009Structural) Dinesh C. Soares, Paul N. Barlow, Helen J. Newbery, David J. Porteous, and Catherine M. Abbott. Structural models of human eef1a1 and eef1a2 reveal two distinct surface clusters of sequence variation and potential differences in phosphorylation. PLoS ONE, 4(7):e6315, July 2009. URL: http://dx.doi.org/10.1371/journal.pone.0006315, doi:10.1371/journal.pone.0006315. (94 citations) 10.1371/journal.pone.0006315](https://doi.org/10.1371/journal.pone.0006315)

[2. (Abbas2015The) Wasim Abbas, Amit Kumar, and Georges Herbein. The eef1a proteins: at the crossroads of oncogenesis, apoptosis, and viral infections. Frontiers in Oncology, April 2015. URL: http://dx.doi.org/10.3389/fonc.2015.00075, doi:10.3389/fonc.2015.00075. (234 citations) 10.3389/fonc.2015.00075](https://doi.org/10.3389/fonc.2015.00075)

[3. (Joung2019Expression) Eun kyo Joung, Jiyoung Kim, Nara Yoon, Lee-so Maeng, Ji Hoon Kim, Sungsoo Park, Keunsoo Kang, Jeong Seon Kim, Young-Ho Ahn, Yoon Ho Ko, Jae Ho Byun, and Ji Hyung Hong. Expression of eef1a1 is associated with prognosis of patients with colon adenocarcinoma. Journal of Clinical Medicine, 8(11):1903, November 2019. URL: http://dx.doi.org/10.3390/jcm8111903, doi:10.3390/jcm8111903. (17 citations) 10.3390/jcm8111903](https://doi.org/10.3390/jcm8111903)

[4. (Morrissey2015The) Catherine Morrissey, David Schwefel, Valerie Ennis-Adeniran, Ian A. Taylor, Yanick J. Crow, and Michelle Webb. The eukaryotic elongation factor eef1a1 interacts with samhd1. Biochemical Journal, 466(1):69–76, February 2015. URL: http://dx.doi.org/10.1042/bj20140203, doi:10.1042/bj20140203. (19 citations) 10.1042/bj20140203](https://doi.org/10.1042/bj20140203)

[5. (Mills2021On) Alberto Mills and Federico Gago. On the need to tell apart fraternal twins eef1a1 and eef1a2, and their respective outfits. International Journal of Molecular Sciences, 22(13):6973, June 2021. URL: http://dx.doi.org/10.3390/ijms22136973, doi:10.3390/ijms22136973. (25 citations) 10.3390/ijms22136973](https://doi.org/10.3390/ijms22136973)

[6. (Li2017Expanded) Li Li, Nelson Ka Lam Ng, Alex Chun Koon, and Ho Yin Edwin Chan. Expanded polyalanine tracts function as nuclear export signals and promote protein mislocalization via eef1a1 factor. Journal of Biological Chemistry, 292(14):5784–5800, April 2017. URL: http://dx.doi.org/10.1074/jbc.m116.763599, doi:10.1074/jbc.m116.763599. (26 citations) 10.1074/jbc.m116.763599](https://doi.org/10.1074/jbc.m116.763599)

[7. (Novosylna2015Translation) Oleksandra Novosylna, Ewelina Jurewicz, Nikolay Pydiura, Agnieszka Goral, Anna Filipek, Boris Negrutskii, and Anna El’skaya. Translation elongation factor eef1a1 is a novel partner of a multifunctional protein sgt1. Biochimie, 119:137–145, December 2015. URL: http://dx.doi.org/10.1016/j.biochi.2015.10.026, doi:10.1016/j.biochi.2015.10.026. (21 citations) 10.1016/j.biochi.2015.10.026](https://doi.org/10.1016/j.biochi.2015.10.026)

[8. (Hassan2018The) Md. Khurshidul Hassan, Dinesh Kumar, Monali Naik, and Manjusha Dixit. The expression profile and prognostic significance of eukaryotic translation elongation factors in different cancers. PLOS ONE, 13(1):e0191377, January 2018. URL: http://dx.doi.org/10.1371/journal.pone.0191377, doi:10.1371/journal.pone.0191377. (90 citations) 10.1371/journal.pone.0191377](https://doi.org/10.1371/journal.pone.0191377)

[9. (Vera2014The) Maria Vera, Bibhusita Pani, Lowri A Griffiths, Christian Muchardt, Catherine M Abbott, Robert H Singer, and Evgeny Nudler. The translation elongation factor eef1a1 couples transcription to translation during heat shock response. eLife, September 2014. URL: http://dx.doi.org/10.7554/elife.03164, doi:10.7554/elife.03164. (168 citations) 10.7554/elife.03164](https://doi.org/10.7554/elife.03164)

[10. (Kanibolotsky2008Multiple) Dmitry S Kanibolotsky, Oleksandra V Novosyl’na, Catherine M Abbott, Boris S Negrutskii, and Anna V El’skaya. Multiple molecular dynamics simulation of the isoforms of human translation elongation factor 1a reveals reversible fluctuations between “open” and “closed” conformations and suggests specific for eef1a1 affinity for ca2+-calmodulin. BMC Structural Biology, January 2008. URL: http://dx.doi.org/10.1186/1472-6807-8-4, doi:10.1186/1472-6807-8-4. (44 citations) 10.1186/1472-6807-8-4](https://doi.org/10.1186/1472-6807-8-4)