SLC31A1 Protein, Human (Cell-Free, His-SUMO)

SLC31A1, a critical uniporter, orchestrates the transport of copper(1+) from the extracellular space into the cytoplasm, traversing the plasma membrane. This transport is facilitated with remarkable specificity, as SLC31A1 directly delivers copper(1+) to specialized chaperones like ATOX1 through a copper(1+)-mediated transient interaction within its C-terminal domain. This intricate process serves as a regulatory mechanism, tightly controlling intracellular copper(1+) levels. Beyond its canonical role, SLC31A1 exhibits versatility by potentially participating in copper(1+) import from the apical membrane, suggesting a role in intestinal copper absorption. The transport mechanism is sodium-independent, highly-affinity driven, and saturable. Furthermore, SLC31A1 mediates the uptake of silver(1+), and its involvement in the influx of platinum-containing chemotherapeutic agents suggests a potential impact on therapeutic responses. In vitro studies demonstrate SLC31A1's ability to transport cadmium(2+) into cells. Remarkably, SLC31A1 acts not only as a copper transporter but also as a redox sensor, promoting angiogenesis in endothelial cells by transmitting VEGF-induced ROS signals. This process involves sulfenylation at Cys-189, leading to disulfide bond formation between SLC31A1 and KDR, facilitating sustained VEGFR2 signaling. The SLC31A1-KDR complex is co-internalized into early endosomes, contributing to prolonged VEGFR2 signaling. Additionally, SLC31A1 mobilizes copper(1+) out of the endosomal compartment, facilitating its availability for export out of cells. These diverse functions underscore the multifaceted nature of SLC31A1 in cellular copper homeostasis and signaling pathways.