General Information of Drug Off-Target (DOT) (ID: OT5BJSEX)

DOT Name Fibrinogen gamma chain (FGG)
Gene Name FGG
Related Disease
Congenital fibrinogen deficiency ( )
Congenital afibrinogenemia ( )
Familial dysfibrinogenemia ( )
Thrombophilia ( )
Familial hypofibrinogenemia ( )
UniProt ID
FIBG_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1DUG ; 1FIB ; 1FIC ; 1FID ; 1FZA ; 1FZB ; 1FZC ; 1FZE ; 1FZF ; 1FZG ; 1LT9 ; 1LTJ ; 1N86 ; 1N8E ; 1RE3 ; 1RE4 ; 1RF0 ; 1RF1 ; 2A45 ; 2FFD ; 2FIB ; 2H43 ; 2HLO ; 2HOD ; 2HPC ; 2HWL ; 2OYH ; 2OYI ; 2Q9I ; 2VDO ; 2VDP ; 2VDQ ; 2VDR ; 2VR3 ; 2XNX ; 2XNY ; 2Y7L ; 2Z4E ; 3BVH ; 3E1I ; 3FIB ; 3GHG ; 3H32 ; 3HUS ; 4B60
Pfam ID
PF08702 ; PF00147
Sequence
MSWSLHPRNLILYFYALLFLSSTCVAYVATRDNCCILDERFGSYCPTTCGIADFLSTYQT
KVDKDLQSLEDILHQVENKTSEVKQLIKAIQLTYNPDESSKPNMIDAATLKSRKMLEEIM
KYEASILTHDSSIRYLQEIYNSNNQKIVNLKEKVAQLEAQCQEPCKDTVQIHDITGKDCQ
DIANKGAKQSGLYFIKPLKANQQFLVYCEIDGSGNGWTVFQKRLDGSVDFKKNWIQYKEG
FGHLSPTGTTEFWLGNEKIHLISTQSAIPYALRVELEDWNGRTSTADYAMFKVGPEADKY
RLTYAYFAGGDAGDAFDGFDFGDDPSDKFFTSHNGMQFSTWDNDNDKFEGNCAEQDGSGW
WMNKCHAGHLNGVYYQGGTYSKASTPNGYDNGIIWATWKTRWYSMKKTTMKIIPFNRLTI
GEGQQHHLGGAKQVRPEHPAETEYDSLYPEDDL
Function
Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. Has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways.
Tissue Specificity Detected in blood plasma (at protein level).
KEGG Pathway
Complement and coagulation cascades (hsa04610 )
Platelet activation (hsa04611 )
Neutrophil extracellular trap formation (hsa04613 )
Staphylococcus aureus infection (hsa05150 )
Coro.virus disease - COVID-19 (hsa05171 )
Reactome Pathway
ER-Phagosome pathway (R-HSA-1236974 )
Common Pathway of Fibrin Clot Formation (R-HSA-140875 )
MyD88 (R-HSA-166058 )
Integrin cell surface interactions (R-HSA-216083 )
Integrin signaling (R-HSA-354192 )
GRB2 (R-HSA-354194 )
p130Cas linkage to MAPK signaling for integrins (R-HSA-372708 )
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426 )
MyD88 deficiency (TLR2/4) (R-HSA-5602498 )
IRAK4 deficiency (TLR2/4) (R-HSA-5603041 )
MAP2K and MAPK activation (R-HSA-5674135 )
Regulation of TLR by endogenous ligand (R-HSA-5686938 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by high-kinase activity BRAF mutants (R-HSA-6802948 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Post-translational protein phosphorylation (R-HSA-8957275 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by RAF1 mutants (R-HSA-9656223 )
Platelet degranulation (R-HSA-114608 )
BioCyc Pathway
MetaCyc:ENSG00000171557-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Congenital fibrinogen deficiency DIS84ZAR Definitive Semidominant [1]
Congenital afibrinogenemia DISGCW8D Strong Autosomal recessive [2]
Familial dysfibrinogenemia DISEOPCW Strong Autosomal dominant [3]
Thrombophilia DISQR7U7 Strong Autosomal dominant [4]
Familial hypofibrinogenemia DIS7WFBL Supportive Autosomal dominant [5]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 Fibrinogen gamma chain (FGG). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Fibrinogen gamma chain (FGG). [20]
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17 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Fibrinogen gamma chain (FGG). [7]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Fibrinogen gamma chain (FGG). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Fibrinogen gamma chain (FGG). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Fibrinogen gamma chain (FGG). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Fibrinogen gamma chain (FGG). [11]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Fibrinogen gamma chain (FGG). [12]
Menadione DMSJDTY Approved Menadione increases the expression of Fibrinogen gamma chain (FGG). [12]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Fibrinogen gamma chain (FGG). [13]
Rosiglitazone DMILWZR Approved Rosiglitazone affects the expression of Fibrinogen gamma chain (FGG). [14]
Malathion DMXZ84M Approved Malathion decreases the expression of Fibrinogen gamma chain (FGG). [15]
Gemcitabine DMSE3I7 Approved Gemcitabine affects the expression of Fibrinogen gamma chain (FGG). [13]
Ursodeoxycholic acid DMCUT21 Approved Ursodeoxycholic acid affects the expression of Fibrinogen gamma chain (FGG). [16]
LY2835219 DM93VBZ Approved LY2835219 decreases the expression of Fibrinogen gamma chain (FGG). [17]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Fibrinogen gamma chain (FGG). [18]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate increases the expression of Fibrinogen gamma chain (FGG). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Fibrinogen gamma chain (FGG). [21]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Fibrinogen gamma chain (FGG). [22]
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⏷ Show the Full List of 17 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
adenosine diphosphate DMFUHKP Investigative adenosine diphosphate increases the secretion of Fibrinogen gamma chain (FGG). [23]
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References

1 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.
2 Congenital fibrinogen disorders: an update. Semin Thromb Hemost. 2013 Sep;39(6):585-95. doi: 10.1055/s-0033-1349222. Epub 2013 Jul 12.
3 A new heterozygous mutation in gamma fibrinogen gene leading to 326 Cys-->Ser substitution in fibrinogen Crdoba is associated with defective polymerization and familial hypodysfibrinogenemia. J Thromb Haemost. 2004 Feb;2(2):352-4. doi: 10.1111/j.1538-7836.2004.0584d.x.
4 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.
5 Congenital hypofibrinogenemia: characterization of two missense mutations affecting fibrinogen assembly and secretion. Blood Cells Mol Dis. 2008 Nov-Dec;41(3):292-7. doi: 10.1016/j.bcmd.2008.06.004. Epub 2008 Aug 3.
6 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.
7 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
8 Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
13 Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
14 Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
15 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
16 Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int. 2008 Aug;28(7):997-1010. doi: 10.1111/j.1478-3231.2008.01744.x. Epub 2008 Apr 15.
17 Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
18 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
19 Induction of fibrinogen and a subset of acute phase response genes involves a novel monokine which is mimicked by phorbol esters. J Biol Chem. 1987 Aug 5;262(22):10850-4.
20 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.
21 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.
22 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.
23 Moderation of the platelet releasate response by aspirin. Blood. 2007 Jun 1;109(11):4786-92. doi: 10.1182/blood-2006-07-038539. Epub 2007 Feb 15.