Protein transport protein Sec61 subunit alpha (SEC61A1)

Protein transport protein Sec61 subunit alpha (Sec61α) is the primary pore-forming subunit of the heterotrimeric Sec61 translocon complex, which is essential for protein biogenesis in the endoplasmic reticulum (ER) [1, 3]. It facilitates the translocation of nascent polypeptides into the ER lumen and the integration of transmembrane proteins into the lipid bilayer, a process critical for roughly one-third of the human proteome [15, 16]. In addition to its transport function, Sec61α acts as a passive calcium leak channel and a ribosome receptor, playing a key role in maintaining cellular calcium homeostasis and regulating the unfolded protein response [4, 6]. Genetic mutations in SEC61A1 lead to "Sec61-channelopathies," manifesting as kidney disease, neutropenia, or immunodeficiency [1, 12]. Pharmacologically, Sec61α is an emerging target for cancer therapy; small-molecule inhibitors like KZR-261 can selectively block the translocation of specific "client" proteins, such as oncogenic growth factors, thereby inducing ER stress and cell death [6, 8]. Furthermore, Sec61α inhibitors exhibit potent antiviral properties by disrupting the production of viral envelope glycoproteins required for the assembly of viruses like SARS-CoV-2 and Ebola [4, 7].

Other names

SEC61A1HSEC61SEC61ASec61 alpha 1Sec61 translocon alpha 1 subunitHNFJ4ADTKD5Protein transport protein Sec61 subunit alpha isoform 1

Inhibition of protein translocation into the endoplasmic reticulum by stabilizing the translocon in a closed state or blocking signal peptide recognition, leading to ER stress and apoptosis.