Details of Drug Off-Target (DOT)

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

• DOT Name: Proline-rich protein 14 (PRR14)
• Gene Name: PRR14
• Related Disease:
  Colon cancer
  Colon carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
• UniProt ID: PRR14_HUMAN
• Pfam ID: PF15386
• Sequence:
  MDLPGDSSPPGQPRLCRQPLTRALWGARSPKRPRLQLPGAPSPLEKASRRVLAVVLEDVM
  AVHMVPVVPSKQTSIPQHHSYHQDPVHRQPPASPPRQAGWSSQARPPDPLCLCREPLSRI
  HRTSSTLRRRSRTTPGPEEGPSQKVDRAPQPTLVVMLEDIASPRPPAEGFIDETPNFIIP
  AQRAEPMRIVRQPTPPPGDLEPPFQPSALPADPLESPPTAPDPALELPSTPPPSSLLRPR
  LSPWGLAPLFRSVRSKLESFADIFLTPNKTPQPPPPSPPMKLELKIAISEAEQSGAAEGT
  ASVSPRPPIRQWRTQDHNTPALLPKPSLGRSYSCPDLGPPGPGTCTWPPAPPQPSRPRPR
  RHTVGGGEMARAPPPPRPCLRKEVFPLGGVGASPSLTTSCSSTASTSFSEPAEPRLGSTK
  GKEPRASKDQVLSEPETKTMGKVSRFRIRRTPARPQLNLTPMGLPRPIRLNKKEFSLEEI
  YTNKNYQSPTTRRTFETIFEEPRERNGTLIFTSSRKLRRAVEFRDSSLPRSRRPSRGVRA
  AGGRTVPPNVAPSPDVGPLLQQRLEELDALLLEEETVDREQPHWT
• Function: Functions in tethering peripheral heterochromatin to the nuclear lamina during interphase, possibly through the interaction with heterochromatin protein CBX5/HP1 alpha. Might play a role in reattaching heterochromatin to the nuclear lamina at mitotic exit. Promotes myoblast differentiation during skeletal myogenesis, possibly by stimulating transcription factor MyoD activity via binding to CBX5/HP1 alpha. Involved in the positive regulation of the PI3K-Akt-mTOR signaling pathway and in promoting cell proliferation, possibly via binding to GRB2.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

7 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 Proline-rich protein 14 (PRR14).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Proline-rich protein 14 (PRR14).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proline-rich protein 14 (PRR14).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Proline-rich protein 14 (PRR14).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Proline-rich protein 14 (PRR14).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Proline-rich protein 14 (PRR14).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Proline-rich protein 14 (PRR14).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Proline-rich protein 14 (PRR14).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Proline-rich protein 14 (PRR14).	[9]

References

• [1] PRR14 overexpression promotes cell growth, epithelial to mesenchymal transition and metastasis of colon cancer via the AKT pathway.PLoS One. 2019 Oct 9;14(10):e0218839. doi: 10.1371/journal.pone.0218839. eCollection 2019.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] 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.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.