Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT11Z3XX)

• DOT Name: Protein PAT1 homolog 1 (PATL1)
• Synonyms: PAT1-like protein 1; Protein PAT1 homolog b; Pat1b; hPat1b
• Gene Name: PATL1
• UniProt ID: PATL1_HUMAN
• PDB ID: 2XEQ; 2XER; 2XES
• Pfam ID: PF09770
• Sequence:
  MFRYESLEDCPLDEDEDAFQGLGEEDEEIDQFNDDTFGSGAVDDDWQEAHERLAELEEKL
  PVAVNEQTGNGERDEMDLLGDHEENLAERLSKMVIENELEDPAIMRAVQTRPVLQPQPGS
  LNSSIWDGSEVLRRIRGPLLAQEMPTVSVLEYALPQRPPQGPEDDRDLSERALPRRSTSP
  IIGSPPVRAVPIGTPPKQMAVPSFTQQILCPKPVHVRPPMPPRYPAPYGERMSPNQLCSV
  PNSSLLGHPFPPSVPPVLSPLQRAQLLGGAQLQPGRMSPSQFARVPGFVGSPLAAMNPKL
  LQGRVGQMLPPAPGFRAFFSAPPSATPPPQQHPPGPGPHLQNLRSQAPMFRPDTTHLHPQ
  HRRLLHQRQQQNRSQHRNLNGAGDRGSHRSSHQDHLRKDPYANLMLQREKDWVSKIQMMQ
  LQSTDPYLDDFYYQNYFEKLEKLSAAEEIQGDGPKKERTKLITPQVAKLEHAYKPVQFEG
  SLGKLTVSSVNNPRKMIDAVVTSRSEDDETKEKQVRDKRRKTLVIIEKTYSLLLDVEDYE
  RRYLLSLEEERPALMDDRKHKICSMYDNLRGKLPGQERPSDDHFVQIMCIRKGKRMVARI
  LPFLSTEQAADILMTTARNLPFLIKKDAQDEVLPCLLSPFSLLLYHLPSVSITSLLRQLM
  NLPQSAATPALSNPHLTAVLQNKFGLSLLLILLSRGEDLQSSDPATESTQNNQWTEVMFM
  ATRELLRIPQAALAKPISIPTNLVSLFSRYVDRQKLNLLETKLQLVQGIR
• Function: RNA-binding protein involved in deadenylation-dependent decapping of mRNAs, leading to the degradation of mRNAs. Acts as a scaffold protein that connects deadenylation and decapping machinery. Required for cytoplasmic mRNA processing body (P-body) assembly ; (Microbial infection) In case of infection, required for translation and replication of hepatitis C virus (HCV).
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: R. degradation (hsa03018)
• Reactome Pathway: mRNA decay by 5' to 3' exoribonuclease (R-HSA-430039)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Protein PAT1 homolog 1 (PATL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein PAT1 homolog 1 (PATL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein PAT1 homolog 1 (PATL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein PAT1 homolog 1 (PATL1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein PAT1 homolog 1 (PATL1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein PAT1 homolog 1 (PATL1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein PAT1 homolog 1 (PATL1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein PAT1 homolog 1 (PATL1).	[1]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein PAT1 homolog 1 (PATL1).	[9]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein PAT1 homolog 1 (PATL1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein PAT1 homolog 1 (PATL1).	[12]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Protein PAT1 homolog 1 (PATL1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein PAT1 homolog 1 (PATL1).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein PAT1 homolog 1 (PATL1).	[15]

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 Protein PAT1 homolog 1 (PATL1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein PAT1 homolog 1 (PATL1).	[11]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] 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.
• [9] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [11] 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.
• [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] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.