Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHR1AOO)

DOT Name Profilin-4 (PFN4)
Synonyms Profilin IV
Gene Name PFN4
UniProt ID
PROF4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00235
Sequence
MSHLQSLLLDTLLGTKHVDSAALIKIQERSLCVASPGFNVTPSDVRTLVNGFAKNPLQAR
REGLYFKGKDYRCVRADEYSLYAKNENTGVVVVKTHLYLLVATYTEGMYPSICVEATESL
GDYLRKKGS
Function
Involved in male fertility. Required for manchette development and acrosome biogenesis during spermiogenesis. Binds in vitro to phospholipids, including phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidic acid (PA). Contrary to other profilin family members, does not bind to actin in vitro.
Tissue Specificity Expressed in testis, in germ cells in seminiferous tubules (at protein level) . Prominently expressed in pachytene/diplotene stage spematocytes .
KEGG Pathway
Rap1 sig.ling pathway (hsa04015 )
Regulation of actin cytoskeleton (hsa04810 )
Amyotrophic lateral sclerosis (hsa05014 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Profilin-4 (PFN4). [1]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Profilin-4 (PFN4). [2]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Profilin-4 (PFN4). [5]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Profilin-4 (PFN4). [3]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Profilin-4 (PFN4). [4]
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References

1 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.
2 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
3 Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
4 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.
5 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.