Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGQY66H)

• DOT Name: Retinitis pigmentosa 9 protein (RP9)
• Synonyms: Pim-1-associated protein; PAP-1
• Gene Name: RP9
• Related Disease:
  Advanced cancer
  Carcinoma
  Cervical Intraepithelial neoplasia
  Colitis
  Dysplasia of cervix
  Human papillomavirus infection
  Lipodystrophy
  Neuralgia
  Retinitis pigmentosa 9
  Type-1/2 diabetes
  Retinitis pigmentosa
  Neoplasm
  Non-insulin dependent diabetes
• UniProt ID: RP9_HUMAN
• Sequence:
  MSSRPGREDVGAAGARRPREPPEQELQRRREQKRRRHDAQQLQQLKHLESFYEKPPPGLI
  KEDETKPEDCIPDVPGNEHAREFLAHAPTKGLWMPLGKEVKVMQCWRCKRYGHRTGDKEC
  PFFIKGNQKLEQFRVAHEDPMYDIIRDNKRHEKDVRIQQLKQLLEDSTSDEDRSSSSSSE
  GKEKHKKKKKKEKHKKRKKEKKKKKKRKHKSSKSNEGSDSE
• Function: Is thought to be a target protein for the PIM1 kinase. May play some roles in B-cell proliferation in association with PIM1.
• Tissue Specificity: Appears to be expressed in a wide range of tissues.
• KEGG Pathway: Spliceosome (hsa03040)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[3]
Colitis	DISAF7DD	Strong	Altered Expression	[4]
Dysplasia of cervix	DISOAROS	Strong	Altered Expression	[3]
Human papillomavirus infection	DISX61LX	Strong	Biomarker	[2]
Lipodystrophy	DIS3SGVD	Strong	Biomarker	[5]
Neuralgia	DISWO58J	Strong	Biomarker	[6]
Retinitis pigmentosa 9	DISHLM3S	Strong	Autosomal dominant	[7]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[8]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[9]
Neoplasm	DISZKGEW	Limited	Biomarker	[10]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[11]

5 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 Retinitis pigmentosa 9 protein (RP9).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Retinitis pigmentosa 9 protein (RP9).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Retinitis pigmentosa 9 protein (RP9).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Retinitis pigmentosa 9 protein (RP9).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Retinitis pigmentosa 9 protein (RP9).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Retinitis pigmentosa 9 protein (RP9).	[17]

References

• [1] Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells.EMBO Mol Med. 2012 Jul;4(7):577-93. doi: 10.1002/emmm.201200235. Epub 2012 Apr 11.
• [2] Detection of human papillomavirus DNA by the hybrid capture assay.Braz J Infect Dis. 2003 Apr;7(2):121-5. doi: 10.1590/s1413-86702003000200004. Epub 2003 Nov 19.
• [3] PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears.Int J Cancer. 1996 Dec 11;68(6):766-9. doi: 10.1002/(SICI)1097-0215(19961211)68:6<766::AID-IJC13>3.0.CO;2-Z.
• [4] PAP-1 ameliorates DSS-induced colitis with involvement of NLRP3 inflammasome pathway.Int Immunopharmacol. 2019 Oct;75:105776. doi: 10.1016/j.intimp.2019.105776. Epub 2019 Jul 24.
• [5] Three mammalian lipins act as phosphatidate phosphatases with distinct tissue expression patterns.J Biol Chem. 2007 Feb 9;282(6):3450-7. doi: 10.1074/jbc.M610745200. Epub 2006 Dec 7.
• [6] Nerve Injury-Induced Neuronal PAP-I Maintains Neuropathic Pain by Activating Spinal Microglia.J Neurosci. 2020 Jan 8;40(2):297-310. doi: 10.1523/JNEUROSCI.1414-19.2019. Epub 2019 Nov 19.
• [7] Mutations in a protein target of the Pim-1 kinase associated with the RP9 form of autosomal dominant retinitis pigmentosa. Eur J Hum Genet. 2002 Apr;10(4):245-9. doi: 10.1038/sj.ejhg.5200797.
• [8] Suppression of cardiac phosphatidate phosphohydrolase 1 activity and lipin mRNA expression in Zucker diabetic fatty rats and humans with type 2 diabetes mellitus.Biochem Biophys Res Commun. 2009 Dec 4;390(1):165-70. doi: 10.1016/j.bbrc.2009.09.108. Epub 2009 Sep 30.
• [9] Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [10] Regulation of Proliferation by a Mitochondrial Potassium Channel in Pancreatic Ductal Adenocarcinoma Cells.Front Oncol. 2017 Sep 29;7:239. doi: 10.3389/fonc.2017.00239. eCollection 2017.
• [11] Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes.Diabetologia. 2016 Sep;59(9):1985-94. doi: 10.1007/s00125-016-4018-0. Epub 2016 Jun 25.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.