General Information of Drug Off-Target (DOT) (ID: OT5WRWRJ)

DOT Name Platelet-derived growth factor D (PDGFD)
Synonyms PDGF-D; Iris-expressed growth factor; Spinal cord-derived growth factor B; SCDGF-B
Gene Name PDGFD
Related Disease
Pulmonary arterial hypertension ( )
UniProt ID
PDGFD_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00431 ; PF00341
Sequence
MHRLIFVYTLICANFCSCRDTSATPQSASIKALRNANLRRDESNHLTDLYRRDETIQVKG
NGYVQSPRFPNSYPRNLLLTWRLHSQENTRIQLVFDNQFGLEEAENDICRYDFVEVEDIS
ETSTIIRGRWCGHKEVPPRIKSRTNQIKITFKSDDYFVAKPGFKIYYSLLEDFQPAAASE
TNWESVTSSISGVSYNSPSVTDPTLIADALDKKIAEFDTVEDLLKYFNPESWQEDLENMY
LDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQ
RCGGNCGCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERC
DCICSSRPPR
Function
Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Plays an important role in wound healing. Induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Can initiate events that lead to a mesangial proliferative glomerulonephritis, including influx of monocytes and macrophages and production of extracellular matrix.
Tissue Specificity
Expressed at high levels in the heart, pancreas, adrenal gland and ovary and at low levels in placenta, liver, kidney, prostate, testis, small intestine, spleen and colon. In the kidney, expressed by the visceral epithelial cells of the glomeruli. A widespread expression is also seen in the medial smooth muscle cells of arteries and arterioles, as well as in smooth muscle cells of vasa rectae in the medullary area. Expressed in the adventitial connective tissue surrounding the suprarenal artery. In chronic obstructive nephropathy, a persistent expression is seen in glomerular visceral epithelial cells and vascular smooth muscle cells, as well as de novo expression by periglomerular interstitial cells and by some neointimal cells of atherosclerotic vessels. Expression in normal prostate is seen preferentially in the mesenchyme of the gland while expression is increased and more profuse in prostate carcinoma. Expressed in many ovarian, lung, renal and brain cancer-derived cell lines.
KEGG Pathway
EGFR tyrosine ki.se inhibitor resistance (hsa01521 )
MAPK sig.ling pathway (hsa04010 )
Ras sig.ling pathway (hsa04014 )
Rap1 sig.ling pathway (hsa04015 )
Calcium sig.ling pathway (hsa04020 )
Phospholipase D sig.ling pathway (hsa04072 )
PI3K-Akt sig.ling pathway (hsa04151 )
Focal adhesion (hsa04510 )
Gap junction (hsa04540 )
Regulation of actin cytoskeleton (hsa04810 )
Prostate cancer (hsa05215 )
Melanoma (hsa05218 )
Choline metabolism in cancer (hsa05231 )
Reactome Pathway
Signaling by PDGF (R-HSA-186797 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Pulmonary arterial hypertension DISP8ZX5 Limited Autosomal dominant [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Platelet-derived growth factor D (PDGFD). [2]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Platelet-derived growth factor D (PDGFD). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Platelet-derived growth factor D (PDGFD). [4]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Platelet-derived growth factor D (PDGFD). [5]
Arsenic DMTL2Y1 Approved Arsenic affects the expression of Platelet-derived growth factor D (PDGFD). [6]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Platelet-derived growth factor D (PDGFD). [7]
Permethrin DMZ0Q1G Approved Permethrin decreases the expression of Platelet-derived growth factor D (PDGFD). [8]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Platelet-derived growth factor D (PDGFD). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Platelet-derived growth factor D (PDGFD). [11]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Platelet-derived growth factor D (PDGFD). [12]
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⏷ Show the Full List of 10 Drug(s)
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 increases the methylation of Platelet-derived growth factor D (PDGFD). [10]
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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 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
3 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.
4 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
5 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
6 Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
7 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
8 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.
9 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
10 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.
11 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
12 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.