Details of Drug Off-Target (DOT)

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

• DOT Name: M-phase phosphoprotein 9 (MPHOSPH9)
• Gene Name: MPHOSPH9
• Related Disease:
  Non-insulin dependent diabetes
  Multiple sclerosis
  Osteoarthritis
  Schizophrenia
  Venous thromboembolism
  Neuroblastoma
• UniProt ID: MPP9_HUMAN
• Sequence:
  MEEFDLVKTLHKTSSSVGSDENSLHSLGLNLNTDRSSPHLSTNGVSSFSGKTRPSVIQGT
  VEVLTSLMQELQNSGKTDSELWKNCETRWLQLFNLVEKQCQEQIVAQQEQFHNQIQHIQE
  EIKNLVKLQTSSASLASCEGNSSNKQVSSESQMGFFSLSSERNESVIHYPESTEPEIQQE
  MSTSQPDCNVDSCSVSSGYGTFCISELNLYKSKDPKEFMEHIDVPKGQYVAPAVPAESLV
  DGVKNENFYIQTPEECHVSLKEDVSISPGEFEHNFLGENKVSEVYSGKTNSNAITSWAQK
  LKQNQPKRAHVEDGGSRSKQGNEQSKKTPIEKSDFAAATHPRAFYLSKPDETPNAWMSDS
  GTGLTYWKLEEKDMHHSLPETLEKTFISLSSTDVSPNQSNTSNEMKLPSLKDIYYKKQRE
  NKQLPERNLTSASNPNHPPEVLTLDPTLHMKPKQQISGIQPHGLPNALDDRISFSPDSVL
  EPSMSSPSDIDSFSQASNVTSQLPGFPKYPSHTKASPVDSWKNQTFQNESRTSSTFPSVY
  TITSNDISVNTVDEENTVMVASASVSQSQLPGTANSVPECISLTSLEDPVILSKIRQNLK
  EKHARHIADLRAYYESEINSLKQKLEAKEISGVEDWKITNQILVDRCGQLDSALHEATSR
  VRTLENKNNLLEIEVNDLRERFSAASSASKILQERIEEMRTSSKEKDNTIIRLKSRLQDL
  EEAFENAYKLSDDKEAQLKQENKMFQDLLGEYESLGKEHRRVKDALNTTENKLLDAYTQI
  SDLKRMISKLEAQVKQVEHENMLSLRHNSRIHVRPSRANTLATSDVSRRKWLIPGAEYSI
  FTGQPLDTQDSNVDNQLEETCSLGHRSPLEKDSSPGSSSTSLLIKKQRETSDTPIMRALK
  ELDEGKIFKNWGTQTEKEDTSNINPRQTETSVNASRSPEKCAQQRQKRLNSASQRSSSLP
  PSNRKSSTPTKREIMLTPVTVAYSPKRSPKENLSPGFSHLLSKNESSPIRFDILLDDLDT
  VPVSTLQRTNPRKQLQFLPLDDSEEKTYSEKATDNHVNHSSCPEPVPNGVKKVSVRTAWE
  KNKSVSYEQCKPVSVTPQGNDFEYTAKIRTLAETERFFDELTKEKDQIEAALSRMPSPGG
  RITLQTRLNQEALEDRLERINRELGSVRMTLKKFHVLRTSANL
• Function: Negatively regulates cilia formation by recruiting the CP110-CEP97 complex (a negative regulator of ciliogenesis) at the distal end of the mother centriole in ciliary cells. At the beginning of cilia formation, MPHOSPH9 undergoes TTBK2-mediated phosphorylation and degradation via the ubiquitin-proteasome system and removes itself and the CP110-CEP97 complex from the distal end of the mother centriole, which subsequently promotes cilia formation.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[1]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[2]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[5]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of M-phase phosphoprotein 9 (MPHOSPH9).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of M-phase phosphoprotein 9 (MPHOSPH9).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[17]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of M-phase phosphoprotein 9 (MPHOSPH9).	[18]

References

• [1] Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies.PLoS One. 2016 Apr 26;11(4):e0154093. doi: 10.1371/journal.pone.0154093. eCollection 2016.
• [2] IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci.Genes Immun. 2010 Jul;11(5):397-405. doi: 10.1038/gene.2010.28. Epub 2010 Jun 17.
• [3] Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019 Feb;51(2):230-236.
• [4] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [5] Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
• [6] Array-based gene expression, CGH and tissue data defines a 12q24 gain in neuroblastic tumors with prognostic implication.BMC Cancer. 2010 May 5;10:181. doi: 10.1186/1471-2407-10-181.
• [7] 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.
• [8] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] 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.
• [11] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [12] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [13] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [14] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [15] 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.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer Cell. 2006 Oct;10(4):321-30.