Details of Drug Off-Target (DOT)

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

• DOT Name: Paralemmin-1 (PALM)
• Synonyms: Paralemmin
• Gene Name: PALM
• Related Disease:
  Anxiety
  Polyp
• UniProt ID: PALM_HUMAN
• Pfam ID: PF03285
• Sequence:
  MEVLAAETTSQQERLQAIAEKRKRQAEIENKRRQLEDERRQLQHLKSKALRERWLLEGTP
  SSASEGDEDLRRQMQDDEQKTRLLEDSVSRLEKEIEVLERGDSAPATAKENAAAPSPVRA
  PAPSPAKEERKTEVVMNSQQTPVGTPKDKRVSNTPLRTVDGSPMMKAAMYSVEITVEKDK
  VTGETRVLSSTTLLPRQPLPLGIKVYEDETKVVHAVDGTAENGIHPLSSSEVDELIHKAD
  EVTLSEAGSTAGAAETRGAVEGAARTTPSRREITGVQAQPGEATSGPPGIQPGQEPPVTM
  IFMGYQNVEDEAETKKVLGLQDTITAELVVIEDAAEPKEPAPPNGSAAEPPTEAASREEN
  QAGPEATTSDPQDLDMKKHRCKCCSIM
• Function: Involved in plasma membrane dynamics and cell process formation. Isoform 1 and isoform 2 are necessary for axonal and dendritic filopodia induction, for dendritic spine maturation and synapse formation in a palmitoylation-dependent manner.
• Tissue Specificity: Widely expressed with highest expression in brain and testis and intermediate expression in heart and adrenal gland.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Genetic Variation	[1]
Polyp	DISRSLYF	Strong	Genetic Variation	[2]

5 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 Paralemmin-1 (PALM).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Paralemmin-1 (PALM).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Paralemmin-1 (PALM).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Paralemmin-1 (PALM).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Paralemmin-1 (PALM).	[14]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Paralemmin-1 (PALM).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Paralemmin-1 (PALM).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Paralemmin-1 (PALM).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Paralemmin-1 (PALM).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Paralemmin-1 (PALM).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Paralemmin-1 (PALM).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Paralemmin-1 (PALM).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Paralemmin-1 (PALM).	[12]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Paralemmin-1 (PALM).	[15]

References

• [1] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [2] Evaluation and Management of Abnormal Uterine Bleeding.Mayo Clin Proc. 2019 Feb;94(2):326-335. doi: 10.1016/j.mayocp.2018.12.012.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] 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.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.