ETS Like-1 protein Elk-1 is a protein that in humans is encoded by the ELK1. Elk-1 functions as a transcription activator. It is classified as a ternary complex factor (TCF), a subclass of the ETS family, which is characterized by a common protein domain that regulates DNA binding to target sequences. Elk1 plays important roles in various contexts, including long-term memory formation, drug addiction, Alzheimer's disease, Down syndrome, breast cancer, and depression. Structure As depicted in Figure 1, the Elk1 protein is composed of several domains. Localized in the N-terminal region, the A domain is required for the binding of Elk1 to DNA. This region also contains a nuclear localization signal (NLS) and a nuclear export signal (NES), which are responsible for nuclear import and export, respectively. The B domain allows Elk1 to bind to a dimer of its cofactor, serum response factor (SRF). Located adjacent to the B domain, the R domain is involved in suppressing Elk1 transcriptional activity. This domain harbors the lysine residues that are likely to undergo SUMOylation, a post-translational event that strengthens the inhibition function of the R domain. The D domain plays the key role of binding to active Mitogen-activated protein kinases (MAPKs). Located in the C-terminal region of Elk1, the C domain includes the amino acids that actually become phosphorylated by MAPKs. In this region, Serine 383 and 389 are key sites that need to be phosphorylated for Elk1-mediated transcription to occur. Finally, the DEF domain is specific for the interaction of activated extracellular signal-regulated kinase (Erk), a type of MAPK, with Elk1. Expression Given its role as a transcription factor, Elk1 is expressed in the nuclei of non-neuronal cells. The protein is present in the cytoplasm as well as in the nucleus of mature neurons. In post-mitotic neurons, a variant of Elk1, sElk1, is expressed solely in the nucleus because it lacks the NES site present in the full-length protein. Moreover, while Elk1 is broadly expressed, actual levels vary among tissues. The rat brain, for example, is extremely rich in Elk1, but the protein is exclusively expressed in neurons. Splice variants Aside from the full-length protein, the Elk1 gene can yield two shortened versions of Elk1: ∆Elk1 and sElk1. Alternative splicing produces ∆Elk1. This variant lacks part of the DNA-binding domain that allows interaction with SRF. On the other hand, sElk1 has an intact region that binds to SRF, but it lacks