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Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review EEF1A2 (eukaryotic translation elongation factor 1 alpha 2) Sanna Noubir, Jonathan M Lee Department of Biochemistry, Microbiology, Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. (SN, JML) Published in Atlas Database: April 2008 Online updated version : http://AtlasGeneticsOncology.org/Genes/EEF1A2ID40408ch20q13.html DOI: 10.4267/2042/44423 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology Expression Identity In mice and humans, eEF1A2 is expressed only in normal tissues of the brain, heart and skeletal muscle. Expression is found in tumours of the breast, lung and ovary. Other names: EEF1AL; EF-1-alpha-2; EF1A; HS1; STN; eEF1A-2 HGNC (Hugo): EEF1A2 Location: 20q13.3 Localisation DNA/RNA Diffusely cytoplasmic and nuclear. Function Description This protein is an isoform of the alpha subunit of the elongation factor-1 complex. There are two known isoforms of protein elongation factor eEF1A (eEF1A1 and eEF1A2). eEF1A proteins are GTP-binding proteins that interact with amino-acylated tRNA and recruit them to the ribosome during the elongation phase of protein translation. In addition, eEF1A2 binds to and stimulates the lipid kinase activity of phosphatidylinositol 4-kinase beta, the enzyme that catalyzes the generation of phospha-tidylinositol 4phosphate from phosphatidylinositol. 8 exons and 7 introns. Transcription 5 alternatives for transcript splicing. Protein Description 50kDa; 463 amino acids contains tRNA binding sites, GTP binding and hydrolysis sites and putative actin binding sites (see figure below). Atlas Genet Cytogenet Oncol Haematol. 2009; 13(3) 196 EEF1A2 (eukaryotic translation elongation factor 1 alpha 2) Noubir S, Lee JM eEF1A2 also activates the Akt serine/threonine kinase and can stimulate actin remodeling and increase the rate of cell invasion and migration in vitro. vitro and also enhances their tumori-genicity in mouse xenograft models. References Homology Anand N, Murthy S, Amann G, Wernick M, Porter LA, Cukier IH, Collins C, Gray JW, Diebold J, Demetrick DJ, Lee JM. Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nat Genet. 2002 Jul;31(3):301-5 EEF1A2 is highly homologous to the EEF1A1. EEF1A2 and EEF1A1 share greater than 90% DNA sequence and amino acid identity. The GTP binding and hydrolysis domains also have homology to the Ras GTPase. Tomlinson VA, Newbery HJ, Wray NR, Jackson J, Larionov A, Miller WR, Dixon JM, Abbott CM. Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours. BMC Cancer. 2005 Sep 12;5:113 Mutations Amiri A, Noei F, Jeganathan S, Kulkarni G, Pinke DE, Lee JM. eEF1A2 activates Akt and stimulates Akt-dependent actin remodeling, invasion and migration. Oncogene. 2007 May 10;26(21):3027-40 Note Inactivation of mouse EEF1A2 leads to immunodeficiency, neuromuscular abnormalities and death by 30 days of age. Jeganathan S, Lee JM. Binding of elongation factor eEF1A2 to phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and phosphatidylinositol 4-phosphate generation. J Biol Chem. 2007 Jan 5;282(1):372-80 Implicated in Tumorigenesis Kulkarni G, Turbin DA, Amiri A, Jeganathan S, AndradeNavarro MA, Wu TD, Huntsman DG, Lee JM. Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer. Breast Cancer Res Treat. 2007 Mar;102(1):3141 Disease Breast, lung and ovarian cancer. EEF1A2 overexpression is found in approximatively 60% of breast, 30% of ovary and 40% of lung tumours. Prognosis High eEF1A2 protein expression is associated with good prognosis in both breast and ovarian cancer. High eEF1A2 protein expression predicts poor prognosis in lung cancer. Cytogenetics Fluorescence in situ hybridization (FISH), showed high copy numbers of EEF1A2 in 25% ovarian tumors. Oncogenesis The eEF1A2 gene is transforming and increases the invitro growth rate of mouse and human cells grown in- Atlas Genet Cytogenet Oncol Haematol. 2009; 13(3) Tomlinson VA, Newbery HJ, Bergmann JH, Boyd J, Scott D, Wray NR, Sellar GC, Gabra H, Graham A, Williams AR, Abbott CM. Expression of eEF1A2 is associated with clear cell histology in ovarian carcinomas: overexpression of the gene is not dependent on modifications at the EEF1A2 locus. Br J Cancer. 2007 May 21;96(10):1613-20 Pinke DE, Kalloger SE, Francetic T, Huntsman DG, Lee JM. The prognostic significance of elongation factor eEF1A2 in ovarian cancer. Gynecol Oncol. 2008 Mar;108(3):561-8 This article should be referenced as such: Noubir S, Lee JM. EEF1A2 (eukaryotic translation elongation factor 1 alpha 2). Atlas Genet Cytogenet Oncol Haematol. 2009; 13(3):196-197. 197