The reference OMIM entry for this protein is 603085

Solute carrier family 31 (copper transporter), member 1; slc31a1
Copper transporter 1; copt1; ctr1

DESCRIPTION

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 (300011) and ATP7B (606882), responsible for the human diseases Menkes syndrome (309400) and Wilson disease (277900), 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 (603088) genes have been identified.

CLONING

Zhou and Gitschier (1997) isolated a human cDNA encoding COPT1, which they called CTR1, by functional complementation of the yeast high-affinity copper uptake mutant ctr1. The deduced 190-amino acid human CTR1 protein is similar to yeast CTR1 and Arabidopsis COPT1, a copper transporter also isolated by functional complementation of yeast ctr1. All 3 predicted proteins have 3 transmembrane domains and an N terminus that is rich in methionine and serine residues; the N terminus of human CTR1 is also abundant in histidines. Northern blot analysis detected 2 major CTR1 transcripts of approximately 2 kb and 5.5 kb and a less abundant transcript of about 8.5 kb in all human organs and tissues examined.

GENE FUNCTION

Zhou and Gitschier (1997) proposed that CTR1 is a high-affinity copper uptake gene because it could complement the yeast ctr1 mutation, it could rescue multiple defects in ctr1 yeast, its expression in ctr1 yeast increased the concentration of cellular copper, and its overexpression in yeast led to a vulnerability to the toxicity of copper overload. Moller et al. (2000) found that cells expressing CTR1 but not those expressing CTR2 showed a dramatic hyperaccumulation of radioactive copper, comparable to that seen in fibroblasts from Menkes disease patients. However, in contrast to the Menkes syndrome fibroblasts, the CTR1-expressing fibroblasts had an efflux rate similar to normal fibroblasts. By cross-linking CTR1 transiently expressed in HEK293 cells, Lee et al. (2002) demonstrated that CTR1 forms a homotrimer as part of a copper transport channel. Functional assays revealed that it stimulates the initial rate of radiolabeled copper uptake. CTR1 transports copper with high affinity in a time-dependent and saturable manner and is copper-specific. Transport is an energy-independent process and is stimulated by extracellular acidic pH and high K+ concentrations. Using pulse-chase labeling followed by immunoprecipitation, Klomp et al. (2002) found that endogenous CTR1 is synthesized in HeLa cells as a 28-kD precursor containing N-linked oligosaccharides, and it is processed into a 35-kD mature protein. Immunofluorescent microscopy showed that the subcellular localization of CTR1 differed between cell types. In some cells, including HeLa, lung, and hepatocellular carcinoma cell lines, it predominantly localized in a vesicular perinuclear compartment, while in other cells, including choriocarcinoma and colon carcinoma cell lines, it localized predominantly at the plasma membrane. The localization of CTR1 was not influenced by copper concentration, but inhibition of endocytosis caused a partial redistribution of CTR1 to the cell surface of HeLa cells. Using accessibility of epitopes to antibody before or after cell permeabilization, Eisses and Kaplan (20 ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 603085 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).