Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1SX3LS)

• DOT Name: Proline and serine-rich protein 2 (PROSER2)
• Gene Name: PROSER2
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: PRSR2_HUMAN
• Pfam ID: PF15385
• Sequence:
  MPVTHRKSDASDMNSDTSPSCRLRAFSRGGSLESRSSSSRSRSFTLDDESLKYLTHEEKD
  VLLFFEETIDSLDEDFEEPVLCDGGVCCLCSPSLEESTSSPSEPEDVIDLVQPAPGAGEA
  EGLPEGTQAAGPAPAGKEHRKQDAETPPPPDPPAPETLLAPPPLPSTPDPPRRELRAPSP
  PVEHPRLLRSVPTPLVMAQKISERMAGNEALSPTSPFREGRPGEWRTPAARGPRSGDPGP
  GPSHPAQPKAPRFPSNIIVTNGAAREPRRTLSRAAVSVQERRAQVLATIHGHAGAFPAAG
  DAGEGAPGGGSSPERVARGRGLPGPAESLRAGGQAPRGPALANGFPSAHEALKSAPSSFA
  PAGKSLCFRPGPALPSTRARQSFPGPRQPNGAQDWRRADSLPRPQGITVQFAGRGSSEEA
  RREALRKLGLLRESS

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Limited	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Proline and serine-rich protein 2 (PROSER2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Proline and serine-rich protein 2 (PROSER2).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Proline and serine-rich protein 2 (PROSER2).	[14]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Proline and serine-rich protein 2 (PROSER2).	[14]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Proline and serine-rich protein 2 (PROSER2).	[16]

12 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 Proline and serine-rich protein 2 (PROSER2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Proline and serine-rich protein 2 (PROSER2).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Proline and serine-rich protein 2 (PROSER2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Proline and serine-rich protein 2 (PROSER2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Proline and serine-rich protein 2 (PROSER2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Proline and serine-rich protein 2 (PROSER2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Proline and serine-rich protein 2 (PROSER2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Proline and serine-rich protein 2 (PROSER2).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Proline and serine-rich protein 2 (PROSER2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Proline and serine-rich protein 2 (PROSER2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Proline and serine-rich protein 2 (PROSER2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Proline and serine-rich protein 2 (PROSER2).	[15]

References

• [1] A lymph node metastasis-related protein-coding genes combining with long noncoding RNA signature for breast cancer survival prediction.J Cell Physiol. 2019 Nov;234(11):20036-20045. doi: 10.1002/jcp.28600. Epub 2019 Apr 4.
• [2] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [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] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [16] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.