Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXLRTUB)

• DOT Name: High affinity copper uptake protein 1 (SLC31A1)
• Synonyms: Copper transporter 1; hCTR1; Solute carrier family 31 member 1
• Gene Name: SLC31A1
• Related Disease: Neurodegeneration and seizures due to copper transport defect
• UniProt ID: COPT1_HUMAN
• PDB ID: 2LS2; 2LS3; 2LS4
• Pfam ID: PF04145
• Sequence:
  MDHSHHMGMSYMDSNSTMQPSHHHPTTSASHSHGGGDSSMMMMPMTFYFGFKNVELLFSG
  LVINTAGEMAGAFVAVFLLAMFYEGLKIARESLLRKSQVSIRYNSMPVPGPNGTILMETH
  KTVGQQMLSFPHLLQTVLHIIQVVISYFLMLIFMTYNGYLCIAVAAGAGTGYFLFSWKKA
  VVVDITEHCH
• Function: [High affinity copper uptake protein 1]: Uniporter that mediates the transport of copper(1+) from the extracellular space to the cytoplasm, across the plasma membrane and delivers directly copper(1+) to specific chaperone such as ATOX1, via a copper(1+)- mediated transient interaction between the C-terminal domain and a copper(1+) chaperone, thus controlling intracellular copper(1+) levels. May function in copper(1+) import from the apical membrane thus may drive intestinal copper absorption. The copper(1+) transport mechanism is sodium-independent, saturable and of high-affinity. Also mediates the uptake of silver(1+). May function in the influx of the platinum-containing chemotherapeutic agents. The platinum-containing chemotherapeutic agents uptake is saturable. In vitro, mediates the transport of cadmium(2+) into cells. Also participates in the first step of copper(2+) acquisition by cells through a direct transfer of copper(2+) from copper(2+) carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper(2+) reduction and probably followed by copper(1+) stabilization. In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper(1+) transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-189 leadin g to a subsequent disulfide bond formation between SLC31A1 and KDR. The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling ; [Truncated CTR1 form]: Mobilizes copper(1+) out of the endosomal compartment, making copper(1+) available for export out of the cells.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  Mineral absorption (hsa04978)
• Reactome Pathway: Metal ion SLC transporters (R-HSA-425410)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurodegeneration and seizures due to copper transport defect	DISO3J1X	Limited	Unknown	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paraquat	DMR8O3X	Investigative	High affinity copper uptake protein 1 (SLC31A1) decreases the response to substance of Paraquat.	[24]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	High affinity copper uptake protein 1 (SLC31A1) affects the uptake of 3-iodothyronamine.	[25]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of High affinity copper uptake protein 1 (SLC31A1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of High affinity copper uptake protein 1 (SLC31A1).	[17]

25 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[10]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[12]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[13]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[14]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[6]
Trientine	DMD2WPG	Approved	Trientine increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[15]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[16]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[15]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[18]
SC-236	DMO1URE	Terminated	SC-236 decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of High affinity copper uptake protein 1 (SLC31A1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of High affinity copper uptake protein 1 (SLC31A1).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[22]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of High affinity copper uptake protein 1 (SLC31A1).	[23]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bortezomib	DMNO38U	Approved	Bortezomib decreases the degradation of High affinity copper uptake protein 1 (SLC31A1).	[11]

References

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