Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2)

Protein transport protein Sec61 subunit alpha isoform 2 (SEC61A2) is a core component of the SEC61 channel-forming translocon complex within the endoplasmic reticulum (ER)[1][9][10]. This complex mediates the **translocation of signal peptide–containing precursor polypeptides** across the ER membrane—an essential, conserved process in protein biosynthesis and membrane assembly[2][3][6]. SEC61A2, alongside its paralog SEC61A1, forms the protein-conducting channel with the capacity to function as a major **ribosome receptor and a gated pore**, enabling both co- and post-translational import of polypeptides into the ER[1][2][7]. The channel also provides a route for passive calcium ion (Ca²⁺) leakage from the ER, influencing cellular calcium homeostasis[2]. SEC61A2's role is particularly critical in pancreatic β-cells, where it impacts proinsulin biosynthesis and thereby glucose regulation[5]. Dysfunction of SEC61A2—by mutation, suppression, or pharmacologic inhibition—has been linked to congenital neutropenia, diabetes, and cancer pathogenesis, making it a potential therapeutic target, though safety concerns are extensive given its central cellular function[2][5].

Other names

SEC61A2Sec61 translocon subunit alpha 2Sec61 alpha-2FLJ10578protein transport protein Sec61 subunit alpha isoform 2Sec61 alpha 2 subunitSec61 alpha form 2sec61 alpha-2

Inhibition of protein translocation by blocking the Sec61 channel function (prevents passage of nascent polypeptides into ER, impairs secretory pathway proteins) Disruption of ER calcium homeostasis via Ca²⁺ leak