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1.A.56.1.2
Copper (Cu+) and silver (Ag+) uptake transporter, Ctr1. The trimeric channel Eisses and Kaplan, 2005) forms an oligomeric pore with each subunit displaying 3 TMSs and 2 metal binding motifs (Lee et al., 2007). TMS2 is sufficient to form the trimer and the MXXM motif bind Ag+ (Dong et al. 2015). Ctr1 mediates basolateral uptakes of Cu+ in enterocytes (Zimnicka et al., 2007) and shows copper-dependent internalization and recycling which provides a reversible mechanism for the regulation of cellular copper entry (Molloy and Kaplan, 2009). It acts as a receptor for the two extinct viruses, CERV1 and CERV2 (Soll et al., 2010). Ctrl takes up platinum anticancer drugs, cisplatin and carboplatin (Du et al., 2012). The 3-d structure is known (Yang et al., 2012).  Ctr1 has a low turn over number of about 10 ions/second/trimer (Maryon et al. 2013).  Methionine and histidine residues in the transmembrane domain are essential for transport of copper, but when mutated, they stimulated uptake of cisplatin (Larson et al. 2010).  Plays important roles in the developing embryo as well as in adult ionic homeostasis (Wee et al. 2013). (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells. EGCG inhibits the rapid degradation of CTR1 induced by cisplatin (cDDP). The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer (Wang et al. 2015). Steroid inhibitors may be able to overcome cycplatin resistance (Kadioglu et al. 2015).  Upregulated in colorectal cancer cells (Barresi et al. 2016).

Accession Number:O15431
Protein Name:COP1 aka hCTR1 aka SLC31A1 aka CTR1 aka COPT1
Length:190
Molecular Weight:21091.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:3
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Cu+, Ag+

Cross database links:

DIP-48727N
Genevestigator: O15431 O15431
eggNOG: prNOG17043 NOG323808
HEGENOM: HBG715469 HOG000195393
RefSeq: NP_001850.1   
Entrez Gene ID: 1317   
Pfam: PF04145   
OMIM: 603085  gene
KEGG: hsa:1317    hsa:1317   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005375 F:copper ion transmembrane transporter activity
GO:0006825 P:copper ion transport

References (15)

[1] “hCTR1: a human gene for copper uptake identified by complementation in yeast.”  Zhou B.et.al.   9207117
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[4] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “O-linked glycosylation at threonine 27 protects the copper transporter hCTR1 from proteolytic cleavage in mammalian cells.”  Maryon E.B.et.al.   17525160
[7] “Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture.”  Aller S.G.et.al.   16501047
[8] “hCTR1: a human gene for copper uptake identified by complementation in yeast.”  Zhou B.et.al.   9207117
[9] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[10] “The full-ORF clone resource of the German cDNA consortium.”  Bechtel S.et.al.   17974005
[11] “DNA sequence and analysis of human chromosome 9.”  Humphray S.J.et.al.   15164053
[12] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[13] “Biochemical characterization of the human copper transporter Ctr1.”  Lee J.et.al.   11734551
[14] “O-linked glycosylation at threonine 27 protects the copper transporter hCTR1 from proteolytic cleavage in mammalian cells.”  Maryon E.B.et.al.   17525160
[15] “Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture.”  Aller S.G.et.al.   16501047
Structure:
2LS2   2LS3   2LS4     

External Searches:

  • Search: DB with
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  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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FASTA formatted sequence
1:	MDHSHHMGMS YMDSNSTMQP SHHHPTTSAS HSHGGGDSSM MMMPMTFYFG FKNVELLFSG 
61:	LVINTAGEMA GAFVAVFLLA MFYEGLKIAR ESLLRKSQVS IRYNSMPVPG PNGTILMETH 
121:	KTVGQQMLSF PHLLQTVLHI IQVVISYFLM LIFMTYNGYL CIAVAAGAGT GYFLFSWKKA 
181:	VVVDITEHCH