Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2BLK17)

• DOT Name: Coagulation factor X (F10)
• Synonyms: EC 3.4.21.6; Stuart factor; Stuart-Prower factor
• Gene Name: F10
• Related Disease: Congenital factor X deficiency
• UniProt ID: FA10_HUMAN
• PDB ID: 1C5M ; 1EZQ ; 1F0R ; 1F0S ; 1FAX ; 1FJS ; 1FXY ; 1G2L ; 1G2M ; 1HCG ; 1IOE ; 1IQE ; 1IQF ; 1IQG ; 1IQH ; 1IQI ; 1IQJ ; 1IQK ; 1IQL ; 1IQM ; 1IQN ; 1KSN ; 1LPG ; 1LPK ; 1LPZ ; 1LQD ; 1MQ5 ; 1MQ6 ; 1NFU ; 1NFW ; 1NFX ; 1NFY ; 1P0S ; 1V3X ; 1WU1 ; 1XKA ; 1XKB ; 1Z6E ; 2BMG ; 2BOH ; 2BOK ; 2BQ6 ; 2BQ7 ; 2BQW ; 2CJI ; 2D1J ; 2EI6 ; 2EI7 ; 2EI8 ; 2FZZ ; 2G00 ; 2GD4 ; 2H9E ; 2J2U ; 2J34 ; 2J38 ; 2J4I ; 2J94 ; 2J95 ; 2JKH ; 2P16 ; 2P3F ; 2P3T ; 2P3U ; 2P93 ; 2P94 ; 2P95 ; 2PHB ; 2PR3 ; 2Q1J ; 2RA0 ; 2UWL ; 2UWO ; 2UWP ; 2VH0 ; 2VH6 ; 2VVC ; 2VVU ; 2VVV ; 2VWL ; 2VWM ; 2VWN ; 2VWO ; 2W26 ; 2W3I ; 2W3K ; 2WYG ; 2WYJ ; 2XBV ; 2XBW ; 2XBX ; 2XBY ; 2XC0 ; 2XC4 ; 2XC5 ; 2Y5F ; 2Y5G ; 2Y5H ; 2Y7X ; 2Y7Z ; 2Y80 ; 2Y81 ; 2Y82 ; 3CEN ; 3CS7 ; 3ENS ; 3FFG ; 3HPT ; 3IIT ; 3K9X ; 3KL6 ; 3KQB ; 3KQC ; 3KQD ; 3KQE ; 3LIW ; 3M36 ; 3M37 ; 3Q3K ; 3SW2 ; 3TK5 ; 3TK6 ; 4A7I ; 4BTI ; 4BTT ; 4BTU ; 4Y6D ; 4Y71 ; 4Y76 ; 4Y79 ; 4Y7A ; 4Y7B ; 4ZH8 ; 4ZHA ; 5JQY ; 5JTC ; 5JZ8 ; 5JZU ; 5K0H ; 5VOE ; 5VOF ; 6Q9F ; 6Q9I ; 6RK9 ; 6YYW ; 6YYX ; 6YYY ; 6Z6Q ; 6Z6R ; 7AHU ; 7BMI ; 7BMJ ; 7E6J ; 7TPP ; 7TPQ ; 7YB8 ; 7YB9 ; 7YBB ; 7YBC ; 8EOK
• EC Number: 3.4.21.6
• Pfam ID: PF00008 ; PF14670 ; PF00594 ; PF00089
• Sequence:
  MGRPLHLVLLSASLAGLLLLGESLFIRREQANNILARVTRANSFLEEMKKGHLERECMEE
  TCSYEEAREVFEDSDKTNEFWNKYKDGDQCETSPCQNQGKCKDGLGEYTCTCLEGFEGKN
  CELFTRKLCSLDNGDCDQFCHEEQNSVVCSCARGYTLADNGKACIPTGPYPCGKQTLERR
  KRSVAQATSSSGEAPDSITWKPYDAADLDPTENPFDLLDFNQTQPERGDNNLTRIVGGQE
  CKDGECPWQALLINEENEGFCGGTILSEFYILTAAHCLYQAKRFKVRVGDRNTEQEEGGE
  AVHEVEVVIKHNRFTKETYDFDIAVLRLKTPITFRMNVAPACLPERDWAESTLMTQKTGI
  VSGFGRTHEKGRQSTRLKMLEVPYVDRNSCKLSSSFIITQNMFCAGYDTKQEDACQGDSG
  GPHVTRFKDTYFVTGIVSWGEGCARKGKYGIYTKVTAFLKWIDRSMKTRGLPKAKSHAPE
  VITSSPLK
• Function: Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
• Tissue Specificity: Plasma; synthesized in the liver.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Gamma-carboxylation of protein precursors (R-HSA-159740)
  Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus (R-HSA-159763)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  Defective factor IX causes thrombophilia (R-HSA-9672383)
  Defective cofactor function of FVIIIa variant (R-HSA-9672396)
  Defective F9 variant does not activate FX (R-HSA-9673202)
  Extrinsic Pathway of Fibrin Clot Formation (R-HSA-140834)
• BioCyc Pathway: MetaCyc:HS05000-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital factor X deficiency	DISOBJ20	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID27977313-Compound-29	DMIF7KG	Patented	Coagulation factor X (F10) increases the Coagulation factor decreased ADR of PMID27977313-Compound-29.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Coagulation factor X (F10).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coagulation factor X (F10).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Coagulation factor X (F10).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coagulation factor X (F10).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Coagulation factor X (F10).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Coagulation factor X (F10).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Coagulation factor X (F10).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Coagulation factor X (F10).	[9]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the activity of Coagulation factor X (F10).	[10]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Coagulation factor X (F10).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Coagulation factor X (F10).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Coagulation factor X (F10).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Coagulation factor X (F10).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Coagulation factor X (F10).	[16]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Coagulation factor X (F10).	[17]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the activity of Coagulation factor X (F10).	[18]
MANGIFERIN	DMWAF5Z	Investigative	MANGIFERIN decreases the activity of Coagulation factor X (F10).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Coagulation factor X (F10).	[14]

References

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• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
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• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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• [7] Progestins regulate genes that can elicit both proliferative and antiproliferative effects in breast cancer cells. Oncol Rep. 2008 Jun;19(6):1627-34.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [10] Comparison of antithrombotic efficacy and haemorrhagic side-effects of Clivarin versus enoxaparin in patients undergoing total hip replacement surgery. Blood Coagul Fibrinolysis. 1993 Dec;4 Suppl 1:S33-5; discussion S37-8.
• [11] Vascular complications of long-term oestrogen therapy. Front Horm Res. 1977;5:174-91. doi: 10.1159/000401993.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [17] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [18] Investigation of the anticoagulant and antithrombotic effects of chlorogenic acid. J Biochem Mol Toxicol. 2017 Mar;31(3). doi: 10.1002/jbt.21865. Epub 2016 Oct 5.
• [19] Polysulfated xanthones: multipathway development of a new generation of dual anticoagulant/antiplatelet agents. J Med Chem. 2011 Aug 11;54(15):5373-84. doi: 10.1021/jm2006589. Epub 2011 Jul 18.
• [20] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.