Eef1akmt2, also known as METTL10, is a lysine methyltransferase that methylates the translation elongation factor eEF1A1. This methylation process is likely involved in the regulation of protein translation pathways, which are fundamental for the synthesis of proteins within cells, thus being of great biological importance. Genetic models, such as knockout models, can be valuable in further elucidating its functions [2].

In SETD2-mutated clear cell renal cell carcinoma (ccRCC), there is a loss of Eef1akmt2 gene expression. SETD2, which is commonly mutated in ccRCC, is responsible for the methylation of histone H3 and non-histone proteins like eEF1A1. The expression of Eef1akmt2 (along with Eef1akmt3) is dependent on the SET-domain function of SETD2. SETD2-KO kidney cells show decreased lysine methylation of eEF1A1 and differential expression of hundreds of proteins, including an increase in many related to protein translation. SETD2-mutated tumors with predicted loss of SET-domain function also have decreased progression-free survival [1].

In summary, Eef1akmt2 plays a role in the methylation of eEF1A1, which is crucial for protein translation. The loss of Eef1akmt2 gene expression in SETD2-mutated ccRCC tumors, as revealed by studies on SETD2-KO kidney cells, suggests its importance in the dysregulation of protein translation in this disease, highlighting its potential significance in understanding the transformed phenotype of ccRCC [1].

References:

1. Hapke, Robert, Venton, Lindsay, Rose, Kristie Lindsay, Rathmell, W Kimryn, Haake, Scott M. 2022. SETD2 regulates the methylation of translation elongation factor eEF1A1 in clear cell renal cell carcinoma. In Kidney cancer journal : official journal of the Kidney Cancer Association, 6, 179-193. doi:10.3233/kca-220009. https://pubmed.ncbi.nlm.nih.gov/36684483/

2. Hamey, Joshua J, Nguyen, Amy, Haddad, Mahdi, Pfeiffer, Paige G, Wilkins, Marc R. 2024. Methylation of elongation factor 1A by yeast Efm4 or human eEF1A-KMT2 involves a beta-hairpin recognition motif and crosstalks with phosphorylation. In The Journal of biological chemistry, 300, 105639. doi:10.1016/j.jbc.2024.105639. https://pubmed.ncbi.nlm.nih.gov/38199565/