SLC31A1
Description
The SLC31A1 (solute carrier family 31 member 1) is a protein-coding gene located on chromosome 9.
High affinity copper uptake protein 1 (CTR1) is a protein that in humans is encoded by the SLC31A1 gene. Copper is an element essential for life, but excessive copper can be toxic or even lethal to the cell. Therefore, cells have developed sophisticated ways to maintain a critical copper balance, with the intake, export, and intracellular compartmentalization or buffering of copper strictly regulated. The 2 related genes ATP7A and ATP7B, responsible for the human diseases Menkes syndrome and Wilson disease, respectively, are involved in copper export. In S. cerevisiae, the copper uptake genes CTR1, CTR2, and CTR3 have been identified, and in human the CTR1 and CTR2 (MIM 603088) genes have been identified.
== Clinical significance == In 2022, a new autosomal-recessive disease was discovered that is caused by mutations of the CTR1 gene. The disease is characterized by profound deficiency of copper in the central nervous system and presents with infantile seizures and neurodegeneration.
== See also == Solute carrier family
== References ==
== Further reading ==
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
SLC31A1 is a uniporter that transports copper(1+) from the extracellular space to the cytoplasm, crossing the plasma membrane. It delivers copper(1+) directly to specific chaperones, like ATOX1, through a transient interaction between its C-terminal domain and a copper(1+) chaperone, thus regulating intracellular copper(1+) levels. It may also facilitate copper(1+) import from the apical membrane, potentially driving intestinal copper absorption. The copper(1+) transport mechanism is sodium-independent, saturable, and of high affinity. SLC31A1 can also mediate the uptake of silver(1+) and may be involved in the influx of platinum-containing chemotherapeutic agents. The platinum-containing chemotherapeutic agents uptake is saturable. In vitro, SLC31A1 mediates the transport of cadmium(2+) into cells. SLC31A1 participates in the initial step of copper(2+) acquisition by cells through direct transfer of copper(2+) from blood copper(2+) carriers, such as albumin (ALB), to its N-terminal domain. This leads to copper(2+) reduction and likely subsequent copper(1+) stabilization. Additionally, SLC31A1 functions as a redox sensor to promote angiogenesis in endothelial cells. It does this independently of copper(1+) transport by transmitting the VEGF-induced ROS signal through sulfenylation at Cys-189, leading to disulfide bond formation between SLC31A1 and KDR. This SLC31A1-KDR complex is then co-internalized to early endosomes, driving sustained VEGFR2 signaling. SLC31A1 mobilizes copper(1+) out of the endosomal compartment, making it available for export from the cells.
SLC31A1 is also known as COPT1, CTR1, NSCT.
