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Gene Review

SLC31A2  -  solute carrier family 31 (copper...

Homo sapiens

Synonyms: COPT2, CTR2, Copper transporter 2, Solute carrier family 31 member 2, hCTR2
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Disease relevance of SLC31A2

  • Recently, the gene underlying Wilson disease (ATP7B) as well as copper transport genes hCTR1, hCTR2 and ATOX1 have been excluded as candidates for NICC in man and copper toxicosis in Bedlington terriers [1].

High impact information on SLC31A2

  • An additional human gene similar to hCTR1, here named hCTR2, was identified in a database search [2].
  • Transfections with increasing concentrations of the G(s) protein-coupled human calcitonin receptor type 2 (hCTR2) cDNA produced sufficient levels of constitutively activated receptor to cause elevated basal cellular responses [3].
  • We isolated two variants of a seven-transmembrane receptor that were identical to two previously described human calcitonin receptors (hCTR1 and hCTR2) [4].
  • The first is that amylin is a weak agonist for hCTR2 and that this receptor is unrelated to the amylin receptor found in this cell line [4].
  • In contrast, expression of hCTR2 in COS cells yielded membranes that bound 125I-AC512, 125I-hCAL, and 125I-rAmylin with high affinity [4].

Biological context of SLC31A2

  • The copper transport genes CTR1 and CTR2 were also excluded as candidate genes for CT since they both mapped to canine chromosome region CFA11q22 [5].
  • Domain-selective cell surface biotinylation followed by immunoblotting of streptavidin-agarose-fractionated biotinylated glycoproteins independently confirmed the polarized distribution of FLAG epitope-tagged hCTR-2 in the basolateral domain [6].
  • 3) Both hCTR-2 forms were changed to a similar size of approximately 57-60 kDa by deglycosylation with endoglycosidase F; this size is consistent with that predicted by the amino acid sequence [7].

Other interactions of SLC31A2

  • Specific binding of 125 pM [125I]amylin to cells transfected with hCTR2 alone was 0.9 +/- 0.2 fmol/50,000 cells (n=6), and was increased by 262 +/- 48% (P < 0.005), 73 +/- 26% (P < 0.05) and 338 +/- 57% (P < 0.005) with RAMP1, -2 or -3, respectively [8].
  • Two hCTR isoforms, hCTR1 and hCTR2, give proteins that differ in their structure and signaling pathways [9].

Analytical, diagnostic and therapeutic context of SLC31A2

  • Fluorescence-activated cell-sorting analysis revealed that their cotransfection with CTR2 induced cell surface expression of all three RAMPs, and the three CTR2/RAMP heterodimers mediated equivalent levels of cAMP production in response to hCGRPalpha that were approximately 50-fold greater than were seen with CTR2 alone [10].
  • Data obtained with immunological techniques and cross-linking of radiolabeled salmon CT ([125I]sCT) revealed two forms of hCTR-2 in transfected cells: a larger, mature cell surface receptor (apparent size, 81 kDa) and a smaller, intracellular form (apparent size, 66 kDa) [7].


  1. Non-Indian childhood cirrhosis. Müller, T., van de Sluis, B., Müller, W., Pearson, P., Wijmenga, C. Eur. J. Med. Res. (1999) [Pubmed]
  2. hCTR1: a human gene for copper uptake identified by complementation in yeast. Zhou, B., Gitschier, J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Use of constitutive G protein-coupled receptor activity for drug discovery. Chen, G., Way, J., Armour, S., Watson, C., Queen, K., Jayawickreme, C.K., Chen, W.J., Kenakin, T. Mol. Pharmacol. (2000) [Pubmed]
  4. Expression cloning and receptor pharmacology of human calcitonin receptors from MCF-7 cells and their relationship to amylin receptors. Chen, W.J., Armour, S., Way, J., Chen, G., Watson, C., Irving, P., Cobb, J., Kadwell, S., Beaumont, K., Rimele, T., Kenakin, T. Mol. Pharmacol. (1997) [Pubmed]
  5. Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16. van de Sluis, B.J., Breen, M., Nanji, M., van Wolferen, M., de Jong, P., Binns, M.M., Pearson, P.L., Kuipers, J., Rothuizen, J., Cox, D.W., Wijmenga, C., van Oost, B.A. Hum. Mol. Genet. (1999) [Pubmed]
  6. Human calcitonin receptor is directly targeted to and retained in the basolateral surface of MDCK cells. Nussenzveig, D.R., Matos, M.D., Thaw, C.N. Am. J. Physiol. (1998) [Pubmed]
  7. Intracellular retention and rapid degradation of human calcitonin receptors overexpressed in COS cells. Dermer, S.J., Cohen, D.P., Thaw, C.N., Nussenzveig, D.R., Gershengorn, M.C. Endocrinology (1996) [Pubmed]
  8. An amylin receptor is revealed following co-transfection of a calcitonin receptor with receptor activity modifying proteins-1 or -3. Muff, R., Bühlmann, N., Fischer, J.A., Born, W. Endocrinology (1999) [Pubmed]
  9. Calcitonin receptor mRNA in mononuclear leucocytes from postmenopausal women: decrease during osteoporosis and link to bone markers with specific isoform involvement. Beaudreuil, J., Taboulet, J., Orcel, P., Graulet, A.M., Denne, M.A., Baudoin, C., Jullienne, A., De Vernejoul, M.C. Bone (2000) [Pubmed]
  10. Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins. Kuwasako, K., Cao, Y.N., Nagoshi, Y., Tsuruda, T., Kitamura, K., Eto, T. Mol. Pharmacol. (2004) [Pubmed]
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