Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0UFQBZ)

• DOT Name: Suppressor of SWI4 1 homolog (PPAN)
• Synonyms: Ssf-1; Brix domain-containing protein 3; Peter Pan homolog
• Gene Name: PPAN
• Related Disease:
  Rheumatoid arthritis
  Acute myocardial infarction
  Advanced cancer
  Astrocytoma
  Lung adenocarcinoma
  Narcolepsy
  Narcolepsy 1
  Oropharyngeal carcinoma
  Clear cell renal carcinoma
  Coronary atherosclerosis
  Hepatocellular carcinoma
  Myocardial ischemia
• UniProt ID: SSF1_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS
• Pfam ID: PF04427
• Sequence:
  MGQSGRSRHQKRARAQAQLRNLEAYAANPHSFVFTRGCTGRNIRQLSLDVRRVMEPLTAS
  RLQVRKKNSLKDCVAVAGPLGVTHFLILSKTETNVYFKLMRLPGGPTLTFQVKKYSLVRD
  VVSSLRRHRMHEQQFAHPPLLVLNSFGPHGMHVKLMATMFQNLFPSINVHKVNLNTIKRC
  LLIDYNPDSQELDFRHYSIKVVPVGASRGMKKLLQEKFPNMSRLQDISELLATGAGLSES
  EAEPDGDHNITELPQAVAGRGNMRAQQSAVRLTEIGPRMTLQLIKVQEGVGEGKVMFHSF
  VSKTEEELQAILEAKEKKLRLKAQRQAQQAQNVQRKQEQREAHRKKSLEGMKKARVGGSD
  EEASGIPSRTASLELGEDDDEQEDDDIEYFCQAVGEAPSEDLFPEAKQKRLAKSPGRKRK
  RWEMDRGRGRLCDQKFPKTKDKSQGAQARRGPRGASRDGGRGRGRGRPGKRVA
• Function: May have a role in cell growth.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[2]
Astrocytoma	DISL3V18	Strong	Genetic Variation	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Narcolepsy	DISLCNLI	Strong	Altered Expression	[5]
Narcolepsy 1	DISTYYJ6	Strong	Genetic Variation	[6]
Oropharyngeal carcinoma	DIS7K3AI	Strong	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	moderate	Genetic Variation	[8]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[10]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[9]

3 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 Suppressor of SWI4 1 homolog (PPAN).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Suppressor of SWI4 1 homolog (PPAN).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Suppressor of SWI4 1 homolog (PPAN).	[21]

11 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 Suppressor of SWI4 1 homolog (PPAN).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Suppressor of SWI4 1 homolog (PPAN).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Suppressor of SWI4 1 homolog (PPAN).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Suppressor of SWI4 1 homolog (PPAN).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Suppressor of SWI4 1 homolog (PPAN).	[17]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Suppressor of SWI4 1 homolog (PPAN).	[18]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Suppressor of SWI4 1 homolog (PPAN).	[19]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Suppressor of SWI4 1 homolog (PPAN).	[19]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Suppressor of SWI4 1 homolog (PPAN).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Suppressor of SWI4 1 homolog (PPAN).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Suppressor of SWI4 1 homolog (PPAN).	[22]

References

• [1] P2Y11 receptor antagonist NF340 ameliorates inflammation in human fibroblast-like synoviocytes: An implication in rheumatoid arthritis.IUBMB Life. 2019 Oct;71(10):1552-1560. doi: 10.1002/iub.2077. Epub 2019 Jul 13.
• [2] Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y11.Eur Heart J. 2007 Jan;28(1):13-8. doi: 10.1093/eurheartj/ehl410. Epub 2006 Nov 29.
• [3] Alanine-(87)-threonine polymorphism impairs signaling and internalization of the human P2Y11 receptor, when co-expressed with the P2Y1 receptor.J Neurochem. 2014 May;129(4):602-13. doi: 10.1111/jnc.12666. Epub 2014 Feb 13.
• [4] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [5] Altered surface expression of P2Y11 receptor with narcolepsy-associated mutations.Pharmacol Rep. 2019 Oct;71(5):926-928. doi: 10.1016/j.pharep.2019.05.005. Epub 2019 May 14.
• [6] EIF3G is associated with narcolepsy across ethnicities.Eur J Hum Genet. 2015 Nov;23(11):1573-80. doi: 10.1038/ejhg.2015.4. Epub 2015 Feb 11.
• [7] Accuracy of the HPV status site-specific factor 10 (SSF-10) variable for patients with oropharyngeal cancers in the Iowa Cancer Registry, 2010-2014.Head Neck. 2018 Oct;40(10):2199-2209. doi: 10.1002/hed.25314. Epub 2018 Jun 22.
• [8] Role of MR texture analysis in histological subtyping and grading of renal cell carcinoma: a preliminary study.Abdom Radiol (NY). 2019 Oct;44(10):3336-3349. doi: 10.1007/s00261-019-02122-z.
• [9] Stimulation of murine P2Y11-like purinoreceptor protects against hypoxia/reoxygenation injury and decreases heart graft rejection lesions.J Thorac Cardiovasc Surg. 2019 Sep;158(3):780-790.e1. doi: 10.1016/j.jtcvs.2018.12.014. Epub 2018 Dec 21.
• [10] Carcinoma-specific expression of P2Y11 receptor and its contribution in ATP-induced purinergic signalling and cell migration in human hepatocellular carcinoma cells.Oncotarget. 2017 Jun 6;8(23):37278-37290. doi: 10.18632/oncotarget.16191.
• [11] 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.
• [12] 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.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] 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.
• [22] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.