Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT41PEMS)

• DOT Name: Serotransferrin (TF)
• Synonyms: Transferrin; Beta-1 metal-binding globulin; Siderophilin
• Gene Name: TF
• Related Disease: Atransferrinemia
• UniProt ID: TRFE_HUMAN
• PDB ID: 1A8E ; 1A8F ; 1B3E ; 1BP5 ; 1BTJ ; 1D3K ; 1D4N ; 1DTG ; 1FQE ; 1FQF ; 1JQF ; 1N7W ; 1N7X ; 1N84 ; 1OQG ; 1OQH ; 1RYO ; 1SUV ; 2HAU ; 2HAV ; 2O7U ; 2O84 ; 3FGS ; 3QYT ; 3S9L ; 3S9M ; 3S9N ; 3SKP ; 3V83 ; 3V89 ; 3V8X ; 3VE1 ; 4H0W ; 4X1B ; 4X1D ; 5DYH ; 5H52 ; 5WTD ; 5X5P ; 5Y6K ; 6CTC ; 6D03 ; 6D04 ; 6D05 ; 6JAS ; 6SOY ; 6SOZ ; 6UJ6 ; 7FFM ; 7FFU ; 7Q1L ; 8BRC
• Pfam ID: PF00405
• Sequence:
  MRLAVGALLVCAVLGLCLAVPDKTVRWCAVSEHEATKCQSFRDHMKSVIPSDGPSVACVK
  KASYLDCIRAIAANEADAVTLDAGLVYDAYLAPNNLKPVVAEFYGSKEDPQTFYYAVAVV
  KKDSGFQMNQLRGKKSCHTGLGRSAGWNIPIGLLYCDLPEPRKPLEKAVANFFSGSCAPC
  ADGTDFPQLCQLCPGCGCSTLNQYFGYSGAFKCLKDGAGDVAFVKHSTIFENLANKADRD
  QYELLCLDNTRKPVDEYKDCHLAQVPSHTVVARSMGGKEDLIWELLNQAQEHFGKDKSKE
  FQLFSSPHGKDLLFKDSAHGFLKVPPRMDAKMYLGYEYVTAIRNLREGTCPEAPTDECKP
  VKWCALSHHERLKCDEWSVNSVGKIECVSAETTEDCIAKIMNGEADAMSLDGGFVYIAGK
  CGLVPVLAENYNKSDNCEDTPEAGYFAVAVVKKSASDLTWDNLKGKKSCHTAVGRTAGWN
  IPMGLLYNKINHCRFDEFFSEGCAPGSKKDSSLCKLCMGSGLNLCEPNNKEGYYGYTGAF
  RCLVEKGDVAFVKHQTVPQNTGGKNPDPWAKNLNEKDYELLCLDGTRKPVEEYANCHLAR
  APNHAVVTRKDKEACVHKILRQQQHLFGSNVTDCSGNFCLFRSETKDLLFRDDTVCLAKL
  HDRNTYEKYLGEEYVKAVGNLRKCSTSSLLEACTFRRP
• Function: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.; (Microbial infection) Serves as an iron source for Neisseria species, which capture the protein and extract its iron for their own use; (Microbial infection) Serves as an iron source for parasite T.brucei (strain 427), which capture TF via its own transferrin receptor ESAG6:ESAG7 and extract its iron for its own use.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• KEGG Pathway:
  HIF-1 sig.ling pathway (hsa04066)
  Ferroptosis (hsa04216)
  TGF-beta sig.ling pathway (hsa04350)
  Mineral absorption (hsa04978)
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Iron uptake and transport (R-HSA-917937)
  Transferrin endocytosis and recycling (R-HSA-917977)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atransferrinemia	DISP0GWY	Strong	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aluminium	DM6ECN9	Approved	Serotransferrin (TF) increases the uptake of Aluminium.	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triamcinolone	DM98IXF	Approved	Serotransferrin (TF) increases the Malignant melanoma ADR of Triamcinolone.	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serotransferrin (TF).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serotransferrin (TF).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serotransferrin (TF).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serotransferrin (TF).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Serotransferrin (TF).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Serotransferrin (TF).	[2]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Serotransferrin (TF).	[8]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Serotransferrin (TF).	[9]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Serotransferrin (TF).	[10]
Prednisolone	DMQ8FR2	Approved	Prednisolone increases the expression of Serotransferrin (TF).	[11]
Clofibrate	DMPC1J7	Approved	Clofibrate increases the expression of Serotransferrin (TF).	[12]
Busulfan	DMXYJ9C	Approved	Busulfan increases the expression of Serotransferrin (TF).	[13]
Deferiprone	DMS2M7O	Approved	Deferiprone increases the expression of Serotransferrin (TF).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Serotransferrin (TF).	[17]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Serotransferrin (TF).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serotransferrin (TF).	[20]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the activity of Serotransferrin (TF).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serotransferrin (TF).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Serotransferrin (TF).	[23]
splitomicin	DMCLHZ5	Investigative	splitomicin increases the activity of Serotransferrin (TF).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the binding of Serotransferrin (TF).	[6]
Isoflurophate	DMBSK7X	Approved	Isoflurophate affects the binding of Serotransferrin (TF).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the secretion of Serotransferrin (TF).	[16]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine affects the localization of Serotransferrin (TF).	[18]
Manganese	DMKT129	Investigative	Manganese affects the binding of Serotransferrin (TF).	[24]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the uptake of Serotransferrin (TF).	[25]
Chlorphrifos oxon	DMGBT68	Investigative	Chlorphrifos oxon affects the binding of Serotransferrin (TF).	[14]

References

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• [12] Effect of clofibrate on plasma proteins including components of the hemostatic mechanism. Clin Chim Acta. 1976 Jan 2;66(1):9-17. doi: 10.1016/0009-8981(76)90366-1.
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• [15] Antiproliferative effect of deferiprone on the Hep G2 cell line. Biochem Pharmacol. 1998 Aug 15;56(4):431-7. doi: 10.1016/s0006-2952(98)00071-9.
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• [17] Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol Cancer Ther. 2005 Feb;4(2):233-41.
• [18] Copper-stimulated endocytosis and degradation of the human copper transporter, hCtr1. J Biol Chem. 2003 Mar 14;278(11):9639-46. doi: 10.1074/jbc.M209455200. Epub 2002 Dec 25.
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• [21] Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen. Breast Cancer Res Treat. 2010 Jan;119(2):283-93. doi: 10.1007/s10549-009-0345-x. Epub 2009 Feb 24.
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• [23] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [24] Aluminum alters iron and manganese uptake and regulation of surface transferrin receptors in primary rat oligodendrocyte cultures. Brain Res. 1996 May 6;719(1-2):72-7. doi: 10.1016/0006-8993(96)00087-x.
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