Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV7BX5A)

• DOT Name: M-phase-specific PLK1-interacting protein (MPLKIP)
• Synonyms: TTD non-photosensitive 1 protein
• Gene Name: MPLKIP
• Related Disease:
  Trichothiodystrophy 4, nonphotosensitive
  Epilepsy
  Trichothiodystrophy
  Kaposi sarcoma
  Cardiomyopathy
• UniProt ID: MPLKI_HUMAN
• Pfam ID: PF15502
• Sequence:
  MQRQNFRPPTPPYPGPGGGGWGSGSSFRGTPGGGGPRPPSPRDGYGSPHHTPPYGPRSRP
  YGSSHSPRHGGSFPGGRFGSPSPGGYPGSYSRSPAGSQQQFGYSPGQQQTHPQGSPRTST
  PFGSGRVREKRMSNELENYFKPSMLEDPWAGLEPVSVVDISQQYSNTQTFTGKKGRYFC
• Function: May play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis.
• Tissue Specificity: Expressed at highest levels in liver and kidney; intermediate expression in skeletal muscle, pancreas, heart and placenta; low expression in brain and lung. Expressed in epidermis and hair follicles.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Trichothiodystrophy 4, nonphotosensitive	DIS6XNFT	Definitive	Autosomal recessive	[1]
Epilepsy	DISBB28L	Strong	Genetic Variation	[2]
Trichothiodystrophy	DISOMQD2	Supportive	Autosomal recessive	[3]
Kaposi sarcoma	DISC1H1Z	Disputed	Biomarker	[4]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of M-phase-specific PLK1-interacting protein (MPLKIP).	[13]

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 M-phase-specific PLK1-interacting protein (MPLKIP).	[12]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] Mutations in the TTDN1 gene are associated with a distinct trichothiodystrophy phenotype.J Invest Dermatol. 2015 Mar;135(3):734-741. doi: 10.1038/jid.2014.440. Epub 2014 Oct 7.
• [3] Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
• [4] The interferon-stimulated gene product oligoadenylate synthetase-like protein enhances replication of Kaposi's sarcoma-associated herpesvirus (KSHV) and interacts with the KSHV ORF20 protein.PLoS Pathog. 2018 Mar 2;14(3):e1006937. doi: 10.1371/journal.ppat.1006937. eCollection 2018 Mar.
• [5] Mitral regurgitation as a phenotypic manifestation of nonphotosensitive trichothiodystrophy due to a splice variant in MPLKIP.BMC Med Genet. 2016 Feb 16;17:13. doi: 10.1186/s12881-016-0275-5.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.