Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZDX0N)

• DOT Name: Mitotic interactor and substrate of PLK1 (MISP)
• Synonyms: Mitotic spindle positioning protein
• Gene Name: MISP
• Related Disease:
  Esophageal squamous cell carcinoma
  Familial adenomatous polyposis
• UniProt ID: MISP_HUMAN
• Pfam ID: PF15304
• Sequence:
  MDRVTRYPILGIPQAHRGTGLVLDGDTSYTYHLVCMGPEASGWGQDEPQTWPTDHRAQQG
  VQRQGVSYSVHAYTGQPSPRGLHSENREDEGWQVYRLGARDAHQGRPTWALRPEDGEDKE
  MKTYRLDAGDADPRRLCDLERERWAVIQGQAVRKSSTVATLQGTPDHGDPRTPGPPRSTP
  LEENVVDREQIDFLAARQQFLSLEQANKGAPHSSPARGTPAGTTPGASQAPKAFNKPHLA
  NGHVVPIKPQVKGVVREENKVRAVPTWASVQVVDDPGSLASVESPGTPKETPIEREIRLA
  QEREADLREQRGLRQATDHQELVEIPTRPLLTKLSLITAPRRERGRPSLYVQRDIVQETQ
  REEDHRREGLHVGRASTPDWVSEGPQPGLRRALSSDSILSPAPDARAADPAPEVRKVNRI
  PPDAYQPYLSPGTPQLEFSAFGAFGKPSSLSTAEAKAATSPKATMSPRHLSESSGKPLST
  KQEASKPPRGCPQANRGVVRWEYFRLRPLRFRAPDEPQQAQVPHVWGWEVAGAPALRLQK
  SQSSDLLERERESVLRREQEVAEERRNALFPEVFSPTPDENSDQNSRSSSQASGITGSYS
  VSESPFFSPIHLHSNVAWTVEDPVDSAPPGQRKKEQWYAGINPSDGINSEVLEAIRVTRH
  KNAMAERWESRIYASEEDD
• Function: Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytospkeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Mitotic interactor and substrate of PLK1 (MISP) decreases the response to substance of Arsenic trioxide.	[14]

7 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 Mitotic interactor and substrate of PLK1 (MISP).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitotic interactor and substrate of PLK1 (MISP).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Mitotic interactor and substrate of PLK1 (MISP).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mitotic interactor and substrate of PLK1 (MISP).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Mitotic interactor and substrate of PLK1 (MISP).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Mitotic interactor and substrate of PLK1 (MISP).	[9]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Mitotic interactor and substrate of PLK1 (MISP).	[13]

6 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 Mitotic interactor and substrate of PLK1 (MISP).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mitotic interactor and substrate of PLK1 (MISP).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mitotic interactor and substrate of PLK1 (MISP).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitotic interactor and substrate of PLK1 (MISP).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Mitotic interactor and substrate of PLK1 (MISP).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mitotic interactor and substrate of PLK1 (MISP).	[11]

References

• [1] Cell Signaling Pathway in 12-O-Tetradecanoylphorbol-13-acetate-Induced LCN2 Gene Transcription in Esophageal Squamous Cell Carcinoma.Biomed Res Int. 2017;2017:9592501. doi: 10.1155/2017/9592501. Epub 2017 Oct 2.
• [2] A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed Asymmetric Cell Division.Genetics. 2018 Mar;208(3):1147-1164. doi: 10.1534/genetics.117.300487. Epub 2018 Jan 18.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] 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.
• [14] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.