High affinity copper uptake protein 2 (hCTR2), also known as Solute carrier family 31 member 2 (SLC31A2), COPT2 or CTR2, is a protein that in humans is encoded by the SLC31A2 gene. SLC31A2 consists of 4 exons with a protein-coding transcript of 1785 bps and is translated to a 143 amino acid peptide. The protein is expressed in all organs and tissues examined, with high levels in the liver and kidney. Distinct from CTR1, CTR2 appears to be localized more in the membranes of intracellular organelles such as vacuoles, vesicles, endosomes, and lysosomes in mammalian cells. CTR2 predominantly resides within the intracellular compartment, which is similar to budding yCTR2, fission yeast CTR6 and A. thaliana COPT5. In contrast to CTR1, human CTR2 expression levels do not lead to obvious changes in cellular copper metabolism.
|Basic Information of SLC31A2|
|Protein Name||Probable low affinity copper uptake protein 2|
|Aliases||Copper transporter 2, hCTR2, Solute carrier family 31 member 2, COPT2, CTR2|
|Organism||Homo sapiens (Human)|
The CTR family of proteins plays a major role in copper translocation across the cellular membranes into the cytoplasm in eukaryotes. SLC31A2 is associated with angiogenesis through copper’s modulation of the hypoxia-inducible factor pathway. It is a novel prognostic marker for patients with clear cell renal cell carcinoma both in overall survival (OS) and disease-free survival (DFS) prediction and could be incorporated with other clinical parameters for better patient risk stratification. SLC31A2 expression is also associated with cisplatin resistance. Knock-down of SLC31A2 leads to enhanced uptake of cisplatin.
Fig.1 (a) Genomic location of SLC31A1 and SLC31A2 with putative/known transcription factor binding sites. (b) Primary structure of SLC31A1 and SLC31A2. (c) Representation of the trimerization of SLC31A1 to form a pore to facilitate copper uptake. (Wee, 2013)
The article reveals that CTR2 is a novel prognostic marker for patients with clear cell renal cell carcinoma (ccRCC) both in OS and DFS prediction and could be incorporated with other clinical parameters for better patient risk stratification.
Authors in this group demonstrate that CTR2 is involved in renal cell carcinoma-derived cell cisplatin resistance.
The article reports that the over-expression of CTR2 will increase exchangeable Cu(+) by 150%. CTR2 regulates intracellular copper and sensitivity to cisplatin.
The article reveals that CTR2 regulates the transport of cDDP in part through control of the rate of macropinocytosis by activation of Rac1 and cdc42. It shows that CTR2 regulates endocytosis and controls tumor growth and sensitivity to cisplatin.
The article reports a biochemical, genetic, and phylogenetic comparison of metazoan Ctr1 and Ctr2, providing mechanistic insights into the evolutionary, biochemical, and functional relationships between these two related proteins.
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