General Information of Drug Off-Target (DOT) (ID: OTNVV3ZG)

DOT Name Fibroblast growth factor 4 (FGF4)
Synonyms FGF-4; Heparin secretory-transforming protein 1; HST; HST-1; HSTF-1; Heparin-binding growth factor 4; HBGF-4; Transforming protein KS3
Gene Name FGF4
UniProt ID
FGF4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1IJT
Pfam ID
PF00167
Sequence
MSGPGTAAVALLPAVLLALLAPWAGRGGAAAPTAPNGTLEAELERRWESLVALSLARLPV
AAQPKEAAVQSGAGDYLLGIKRLRRLYCNVGIGFHLQALPDGRIGGAHADTRDSLLELSP
VERGVVSIFGVASRFFVAMSSKGKLYGSPFFTDECTFKEILLPNNYNAYESYKYPGMFIA
LSKNGKTKKGNRVSPTMKVTHFLPRL
Function
Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Required for normal limb and cardiac valve development during embryogenesis. May play a role in embryonic molar tooth bud development via inducing the expression of MSX1, MSX2 and MSX1-mediated expression of SDC1 in dental mesenchyme cells.
KEGG Pathway
MAPK sig.ling pathway (hsa04010 )
Ras sig.ling pathway (hsa04014 )
Rap1 sig.ling pathway (hsa04015 )
Calcium sig.ling pathway (hsa04020 )
PI3K-Akt sig.ling pathway (hsa04151 )
Regulation of actin cytoskeleton (hsa04810 )
Pathways in cancer (hsa05200 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Melanoma (hsa05218 )
Breast cancer (hsa05224 )
Gastric cancer (hsa05226 )
Reactome Pathway
(FGFR2 )
(FGFR3 )
(FGFR4 )
PIP3 activates AKT signaling (R-HSA-1257604 )
Signaling by activated point mutants of FGFR1 (R-HSA-1839122 )
Signaling by activated point mutants of FGFR3 (R-HSA-1839130 )
FGFR4 ligand binding and activation (R-HSA-190322 )
FGFR3c ligand binding and activation (R-HSA-190372 )
FGFR1c ligand binding and activation (R-HSA-190373 )
FGFR2c ligand binding and activation (R-HSA-190375 )
Activated point mutants of FGFR2 (R-HSA-2033519 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
Phospholipase C-mediated cascade (R-HSA-5654219 )
Phospholipase C-mediated cascade (R-HSA-5654221 )
Phospholipase C-mediated cascade (R-HSA-5654227 )
Phospholipase C-mediated cascade (R-HSA-5654228 )
Downstream signaling of activated FGFR1 (R-HSA-5654687 )
SHC-mediated cascade (R-HSA-5654688 )
PI-3K cascade (R-HSA-5654689 )
FRS-mediated FGFR1 signaling (R-HSA-5654693 )
PI-3K cascade (R-HSA-5654695 )
SHC-mediated cascade (R-HSA-5654699 )
FRS-mediated FGFR2 signaling (R-HSA-5654700 )
SHC-mediated cascade (R-HSA-5654704 )
FRS-mediated FGFR3 signaling (R-HSA-5654706 )
PI-3K cascade (R-HSA-5654710 )
FRS-mediated FGFR4 signaling (R-HSA-5654712 )
SHC-mediated cascade (R-HSA-5654719 )
PI-3K cascade (R-HSA-5654720 )
Negative regulation of FGFR1 signaling (R-HSA-5654726 )
Negative regulation of FGFR2 signaling (R-HSA-5654727 )
Negative regulation of FGFR3 signaling (R-HSA-5654732 )
Negative regulation of FGFR4 signaling (R-HSA-5654733 )
Signaling by FGFR2 in disease (R-HSA-5655253 )
Signaling by FGFR1 in disease (R-HSA-5655302 )
Signaling by FGFR3 in disease (R-HSA-5655332 )
FGFRL1 modulation of FGFR1 signaling (R-HSA-5658623 )
RAF/MAP kinase cascade (R-HSA-5673001 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
PI3K Cascade (R-HSA-109704 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Ethinyl estradiol DMODJ40 Approved Fibroblast growth factor 4 (FGF4) increases the Hepatotoxicity ADR of Ethinyl estradiol. [10]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Fibroblast growth factor 4 (FGF4). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Fibroblast growth factor 4 (FGF4). [8]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin affects the expression of Fibroblast growth factor 4 (FGF4). [2]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Fibroblast growth factor 4 (FGF4). [3]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Fibroblast growth factor 4 (FGF4). [4]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of Fibroblast growth factor 4 (FGF4). [5]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Fibroblast growth factor 4 (FGF4). [6]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Fibroblast growth factor 4 (FGF4). [7]
Belinostat DM6OC53 Phase 2 Belinostat increases the expression of Fibroblast growth factor 4 (FGF4). [6]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Fibroblast growth factor 4 (FGF4). [9]
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⏷ Show the Full List of 8 Drug(s)

References

1 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.
2 Molecular characterization of a toxicological tipping point during human stem cell differentiation. Reprod Toxicol. 2020 Jan;91:1-13. doi: 10.1016/j.reprotox.2019.10.001. Epub 2019 Oct 7.
3 Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21737-42. doi: 10.1073/pnas.1007863107. Epub 2010 Nov 22.
4 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.
5 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
6 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
7 Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer. Cancer Manag Res. 2009 Apr 3;1:25-37.
8 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.
9 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
10 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.