Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB83R61)

• DOT Name: Paralemmin-3 (PALM3)
• Gene Name: PALM3
• UniProt ID: PALM3_HUMAN
• Pfam ID: PF03285
• Sequence:
  MAESSLYRQRLEVIAEKRRLQEEIRAARREVEEEKLRVERLKRKSLRERWLMDGAAAVPE
  PSEDPTSKDPQSPEGQAQARIRNLEDSLFTLQSQLQLLQSASTGAQHKPSGRPSWRRQGH
  RPLSQSIVEAGSVGQTDLNKRASLPAGLVGTPPESPSEPREDVLGFLPGPRQVPGAAGDS
  SEANGPCPSPIPTPEQGLSQRAVPSEGRVGEAKGGGVVSVVWEGLRATEDCATGATGPEL
  EAKVEEVVLEAIGDRKGAGSLELPAWVKEDRGIVEVVWEGVGGSDAEAMGEIGRVPEVVQ
  TSSPRLQERLEAAASIEGEDVPQGSPEGDGQGGSGGEEGSFIWVERVTLSEEWEELLVEG
  LEGPEVAGRERGDESPLGAEGAKTGGGEETWEAEKRKAEESMGIGSEEKPGTGRDEAEMS
  PVVERKGGEKKLELESRGSAEKLGTEREGGEEPLGIERKVEGHLRAEKEGDEEKRGAEEE
  EVEEPLGVEKKGGEEEPEATKEPLEAERKGGEETLEAEKRGGEESLETEKTQGTEGDLNL
  EQGSREGSESQAEEMNEAGPPLEANTETRPEKEGPQPQEKPVGALEEEGVKPQTAAEGQG
  PLGDATPLLAETPAPEQPAECQPLLQGEGPSANPSAHPVPTYAPARQPEPSAPTEGEEAS
  GPKQKTCQCCAVM
• Function: ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Paralemmin-3 (PALM3).	[1]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Paralemmin-3 (PALM3).	[2]
Marinol	DM70IK5	Approved	Marinol increases the expression of Paralemmin-3 (PALM3).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Paralemmin-3 (PALM3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Paralemmin-3 (PALM3).	[7]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Paralemmin-3 (PALM3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Paralemmin-3 (PALM3).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Paralemmin-3 (PALM3).	[8]

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] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [3] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.