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SLC31A1 Membrane Protein Introduction

Introduction of SLC31A1

High affinity copper uptake protein 1 (hCTR1), also known as Solute carrier family 31 member 1 (SLC31A1), COPT1 or CTR1, is a protein that in humans is encoded by the SLC31A1 gene. The protein is expressed in all organs and tissues examined, with high levels in the liver and kidney. Subcellular localization of SLC31A1 is distinct in mammalian cell lines. The majority of SLC31A1 in human embryonic kidney (Hek293) cells is localized at the plasma membrane like yCTR1 in yeast. These distribution patterns might be associated with cell-type specific dynamics of CTR1 secretion or recycling between the plasma membrane and intracellular compartments. Excess copper accumulation in cells with over-expressing CTR1 indicates that it is a limiting factor for cellular copper acquisition. A processed gene that is highly homologous to SLC31A1 has been identified as SLC31A1P1; however, over-expression of the putative encoded C-terminal truncated SLC31A1 (95 amino acids) does not enhance copper uptake.

Basic Information of SLC31A1
Protein Name High affinity copper uptake protein 1
Gene Name SLC31A1
Aliases Copper transporter 1, hCTR1, Solute carrier family 31 member 1, COPT1, CTR1
Organism Homo sapiens (Human)
UniProt ID O15431
Transmembrane Times 3
Length (aa) 190
Sequence MDHSHHMGMSYMDSNSTMQPSHHHPTTSASHSHGGGDSSMMMMPMTFYFGFKNVELLFSGLVINTAGEMAGAFVAVFLLAMFYEGLKIARESLLRKSQVSIRYNSMPVPGPNGTILMETHKTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKAVVVDITEHCH

Function of SLC31A1 Membrane Protein

The proteins of CTR family play a major role in copper translocation across the cellular membranes into the cytoplasm in eukaryotes. Slc31a1 heterozygous knockout mice are similar to wild-type control mice in growth and reproduction; however, copper levels in the brain and spleen of the Slc31a1 knockout mice are approximately 50% less than those of control mice. This indicates that both Slc31a1 alleles are necessary for copper uptake in those organs. Intestine-specific Slc31a1 deficiency in mice showed its functional role in copper absorption from the diet.

CTR1 is also an important factor in determining cellular accumulation and toxicity of platinum-based potent and effective anti-cancer drugs, such as cisplatin. In the case of CTR1, cisplatin bound to the extracellular domains could be carried into the intracellular compartment(s) via the CTR1 internalization process where it can be released to the cytoplasm by a mechanism(s) not yet known.

Schematic illustration of the structure, subcellular localization, and function of human CTR1. Fig.1 Schematic illustration of the structure, subcellular localization, and function of human CTR1. (Kim, 2013)

Application of SLC31A1 Membrane Protein in Literature

  1. Sun C., et al. Genetic polymorphism of SLC31A1 is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation. Oncotarget. 2018, 9(35): 23860-23877. PubMed ID: 29844858

    The article reveals that SLC31A1 modulates miRNA-3'UTR interaction and gene expression and can be used as a potential pharmacogenetic biomarker for clinical outcomes of platinum-based chemotherapy in NSCLC patients.

  2. Anchordoquy J.P., et al. The copper transporter (SLC31A1/CTR1) is expressed in bovine spermatozoa and oocytes: Copper in IVF medium improves sperm quality. Theriogenology. 2017, 97: 124-133. PubMed ID: 28583595

    Authors in this group demonstrate that copper in IVF medium can improve sperm quality. The results exhibit the beneficial effect of Cu on sperm quality.

  3. Cui H., et al. Copper transporter 1 in human colorectal cancer cell lines: Effects of endogenous and modified expression on oxaliplatin cytotoxicity. J Inorg Biochem. 2017, 177: 249-258. PubMed ID: 28551160

    The article reports that genetic or pharmacological modification of hCTR1 protein expression may potentiate oxaliplatin sensitivity in some but not all colorectal cancer cell lines.

  4. Akerfeldt M.C., et al. Interactions of cisplatin and the copper transporter CTR1 in human colon cancer cells. J Biol Inorg Chem. 2017, 22(5): 765-774. PubMed ID: 28516214

    The article reveals that cisplatin and the copper transporter CTR1 interact in human colon cancer cells, which highlight the importance of investigating the interaction of cisplatin with other copper proteins.

  5. Logeman B.L., et al. Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2. J Biol Chem. 2017, 292(27): 11531-11546. PubMed ID: 28507097

    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.

SLC31A1 Preparation Options

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Reference

  1. Kim H, et al. (2013). SLC31 (CTR) family of copper transporters in health and disease. Mol Aspects Med. 34(2-3): 561-70.

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