Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGNJ97M)

• DOT Name: Coagulation factor VII (F7)
• Synonyms: EC 3.4.21.21; Proconvertin; Serum prothrombin conversion accelerator; SPCA; Eptacog alfa
• Gene Name: F7
• Related Disease:
  Congenital factor VII deficiency
  Factor VII deficiency
• UniProt ID: FA7_HUMAN
• PDB ID: 1BF9 ; 1CVW ; 1DAN ; 1DVA ; 1F7E ; 1F7M ; 1FAK ; 1FF7 ; 1FFM ; 1J9C ; 1JBU ; 1KLI ; 1KLJ ; 1O5D ; 1QFK ; 1W0Y ; 1W2K ; 1W7X ; 1W8B ; 1WQV ; 1WSS ; 1WTG ; 1WUN ; 1WV7 ; 1YGC ; 1Z6J ; 2A2Q ; 2AEI ; 2AER ; 2B7D ; 2B8O ; 2BZ6 ; 2C4F ; 2EC9 ; 2F9B ; 2FIR ; 2FLB ; 2FLR ; 2PUQ ; 2ZP0 ; 2ZWL ; 2ZZU ; 3ELA ; 3TH2 ; 3TH3 ; 3TH4 ; 4IBL ; 4ISH ; 4ISI ; 4JYU ; 4JYV ; 4JZD ; 4JZE ; 4JZF ; 4NA9 ; 4NG9 ; 4NGA ; 4X8S ; 4X8T ; 4X8U ; 4X8V ; 4YLQ ; 4YT6 ; 4YT7 ; 4Z6A ; 4ZMA ; 4ZXX ; 4ZXY ; 5I46 ; 5L0S ; 5L2Y ; 5L2Z ; 5L30 ; 5PA8 ; 5PA9 ; 5PAA ; 5PAB ; 5PAC ; 5PAE ; 5PAF ; 5PAG ; 5PAI ; 5PAJ ; 5PAK ; 5PAM ; 5PAN ; 5PAO ; 5PAQ ; 5PAR ; 5PAS ; 5PAT ; 5PAU ; 5PAV ; 5PAW ; 5PAX ; 5PAY ; 5PB0 ; 5PB1 ; 5PB2 ; 5PB3 ; 5PB4 ; 5PB5 ; 5PB6 ; 5TQE ; 5TQF ; 5TQG ; 5U6J
• EC Number: 3.4.21.21
• Pfam ID: PF00008 ; PF14670 ; PF00594 ; PF00089
• Sequence:
  MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRRRR
  ANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGS
  CKDQLQSYICFCLPAFEGRNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSL
  LADGVSCTPTVEYPCGKIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGG
  TLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTN
  HDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVL
  NVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTG
  IVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP
• Function: Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.
• Tissue Specificity: Plasma.
• KEGG Pathway: Complement and coagulation cascades (hsa04610)
• Reactome Pathway:
  Extrinsic Pathway of Fibrin Clot Formation (R-HSA-140834)
  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)
  BMAL1 (R-HSA-1368108)
• BioCyc Pathway: MetaCyc:HS00709-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital factor VII deficiency	DISTANVC	Definitive	Autosomal recessive	[1]
Factor VII deficiency	DISKZWAG	Definitive	Autosomal recessive	[2]

14 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 Coagulation factor VII (F7).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coagulation factor VII (F7).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Coagulation factor VII (F7).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Coagulation factor VII (F7).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Coagulation factor VII (F7).	[7]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Coagulation factor VII (F7).	[8]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Coagulation factor VII (F7).	[9]
Warfarin	DMJYCVW	Approved	Warfarin decreases the expression of Coagulation factor VII (F7).	[10]
Morphine	DMRMS0L	Approved	Morphine increases the expression of Coagulation factor VII (F7).	[11]
Mestranol	DMG3F94	Approved	Mestranol increases the expression of Coagulation factor VII (F7).	[12]
Cenestin	DMXQS7K	Approved	Cenestin increases the expression of Coagulation factor VII (F7).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Coagulation factor VII (F7).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Coagulation factor VII (F7).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Coagulation factor VII (F7).	[17]

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 VII (F7).	[15]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] 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.
• [8] Increased levels of activated factor VII and decreased plasma protein S activity and circulating thrombomodulin during use of oral contraceptives. Thromb Haemost. 1996 Nov;76(5):729-34.
• [9] Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma. Br J Cancer. 2010 Jun 29;103(1):52-60.
• [10] Interaction between fenofibrate and warfarin. Ann Pharmacother. 1998 Jul-Aug;32(7-8):765-8. doi: 10.1345/aph.17310.
• [11] Effect of opium addiction on new and traditional cardiovascular risk factors: do duration of addiction and route of administration matter?. Lipids Health Dis. 2008 Nov 3;7:42. doi: 10.1186/1476-511X-7-42.
• [12] Vascular complications of long-term oestrogen therapy. Front Horm Res. 1977;5:174-91. doi: 10.1159/000401993.
• [13] Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a randomized-controlled study and review of the literature. Thromb Res. 2005;116(1):1-13. doi: 10.1016/j.thromres.2004.09.014.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [17] 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.