Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNA96MR)

DOT Name Mothers against decapentaplegic homolog 3 (SMAD3)
Synonyms MAD homolog 3; Mad3; Mothers against DPP homolog 3; hMAD-3; JV15-2; SMAD family member 3; SMAD 3; Smad3; hSMAD3
Gene Name SMAD3
Related Disease
Aneurysm-osteoarthritis syndrome ( )
Familial thoracic aortic aneurysm and aortic dissection ( )
UniProt ID
SMAD3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1MHD; 1MJS; 1MK2; 1OZJ; 1U7F; 2LAJ; 2LB2; 5OD6; 5ODG; 5XOC; 6YIB; 6ZMN
Pfam ID
PF03165 ; PF03166
Sequence
MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNV
NTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEV
CVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETP
PPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYEL
NQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIG
GEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGF
EAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIR
CSSVS
Function
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
KEGG Pathway
FoxO sig.ling pathway (hsa04068 )
Cell cycle (hsa04110 )
Endocytosis (hsa04144 )
Cellular senescence (hsa04218 )
Wnt sig.ling pathway (hsa04310 )
TGF-beta sig.ling pathway (hsa04350 )
Apelin sig.ling pathway (hsa04371 )
Hippo sig.ling pathway (hsa04390 )
Adherens junction (hsa04520 )
Sig.ling pathways regulating pluripotency of stem cells (hsa04550 )
Th17 cell differentiation (hsa04659 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Hepatitis B (hsa05161 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Pathways in cancer (hsa05200 )
Colorectal cancer (hsa05210 )
Pancreatic cancer (hsa05212 )
Chronic myeloid leukemia (hsa05220 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Inflammatory bowel disease (hsa05321 )
Diabetic cardiomyopathy (hsa05415 )
Reactome Pathway
Signaling by Activin (R-HSA-1502540 )
Downregulation of TGF-beta receptor signaling (R-HSA-2173788 )
TGF-beta receptor signaling activates SMADs (R-HSA-2173789 )
Downregulation of SMAD2/3 (R-HSA-2173795 )
SMAD2/SMAD3 (R-HSA-2173796 )
SMAD2/3 Phosphorylation Motif Mutants in Cancer (R-HSA-3304356 )
SMAD4 MH2 Domain Mutants in Cancer (R-HSA-3311021 )
SMAD2/3 MH2 Domain Mutants in Cancer (R-HSA-3315487 )
TGFBR1 KD Mutants in Cancer (R-HSA-3656532 )
Ub-specific processing proteases (R-HSA-5689880 )
RUNX3 regulates CDKN1A transcription (R-HSA-8941855 )
RUNX3 regulates BCL2L11 (BIM) transcription (R-HSA-8952158 )
Interleukin-37 signaling (R-HSA-9008059 )
NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695 )
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes (R-HSA-9615017 )
FOXO-mediated transcription of cell cycle genes (R-HSA-9617828 )
SARS-CoV-1 targets host intracellular signalling and regulatory pathways (R-HSA-9735871 )
Germ layer formation at gastrulation (R-HSA-9754189 )
Formation of axial mesoderm (R-HSA-9796292 )
Formation of definitive endoderm (R-HSA-9823730 )
Signaling by NODAL (R-HSA-1181150 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Aneurysm-osteoarthritis syndrome DISWN1UZ Definitive Autosomal dominant [1]
Familial thoracic aortic aneurysm and aortic dissection DIS069FB Definitive Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 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 Mothers against decapentaplegic homolog 3 (SMAD3). [2]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [13]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Mothers against decapentaplegic homolog 3 (SMAD3). [18]
Dasatinib DMJV2EK Approved Dasatinib decreases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Mothers against decapentaplegic homolog 3 (SMAD3). [27]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Mothers against decapentaplegic homolog 3 (SMAD3). [28]
Acteoside DM0YHKB Terminated Acteoside increases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [29]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [34]
Deguelin DMXT7WG Investigative Deguelin decreases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [35]
D-glucose DMMG2TO Investigative D-glucose increases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [40]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos increases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [43]
N-nonylphenol DMH3OUX Investigative N-nonylphenol decreases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [45]
20-HETE DM5BAJ9 Investigative 20-HETE increases the phosphorylation of Mothers against decapentaplegic homolog 3 (SMAD3). [46]
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⏷ Show the Full List of 13 Drug(s)
33 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [3]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [7]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [8]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [10]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [14]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [15]
Progesterone DMUY35B Approved Progesterone decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [16]
Menadione DMSJDTY Approved Menadione affects the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [17]
Ethanol DMDRQZU Approved Ethanol increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [19]
Irinotecan DMP6SC2 Approved Irinotecan decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [20]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [22]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [23]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [24]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [25]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [30]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [31]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [32]
Milchsaure DM462BT Investigative Milchsaure increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [33]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [9]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [36]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [37]
Paraquat DMR8O3X Investigative Paraquat increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [38]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [39]
geraniol DMS3CBD Investigative geraniol decreases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [41]
QUERCITRIN DM1DH96 Investigative QUERCITRIN increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [42]
Galangin DM5TQ2O Investigative Galangin increases the expression of Mothers against decapentaplegic homolog 3 (SMAD3). [44]
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⏷ Show the Full List of 33 Drug(s)

References

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