Stromal Interaction Molecule 1 (STIM1) is a protein encoded by the STIM1 gene in humans. It plays a crucial role in cellular calcium signaling, particularly in the regulation of store-operated calcium entry (SOCE). This protein is primarily localized in the endoplasmic reticulum (ER) and, to a lesser extent, in the plasma membrane .
STIM1 has a single transmembrane domain and is characterized by its ability to sense calcium levels within the ER. The protein contains an EF-hand domain that binds calcium ions. When the calcium concentration in the ER decreases, STIM1 undergoes a conformational change, leading to its oligomerization and translocation to regions of the ER that are close to the plasma membrane .
The primary function of STIM1 is to act as a calcium sensor within the ER. Upon sensing a decrease in calcium levels, STIM1 clusters and interacts with ORAI1 channels in the plasma membrane, facilitating calcium influx into the cell. This process is essential for various cellular functions, including gene expression, cell migration, and the regulation of the cell cycle .
Recent studies have uncovered a novel function of STIM1 in the DNA damage response. STIM1 translocates to the nucleus in response to DNA damage, where it helps protect cells from endogenous DNA damage and replicative stress. This nuclear function of STIM1 is crucial for maintaining genomic integrity and ensuring proper DNA repair mechanisms .