Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9IFXAX)

• DOT Name: Rho family-interacting cell polarization regulator 1 (RIPOR1)
• Gene Name: RIPOR1
• UniProt ID: RIPR1_HUMAN
• Pfam ID: PF15903
• Sequence:
  MMSLSVRPQRRLLSARVNRSQSFAGVLGSHERGPSLSFRSFPVFSPPGPPRKPPALSRVS
  RMFSVAHPAAKVPQPERLDLVYTALKRGLTAYLEVHQQEQEKLQGQIRESKRNSRLGFLY
  DLDKQVKSIERFLRRLEFHASKIDELYEAYCVQRRLRDGAYNMVRAYTTGSPGSREARDS
  LAEATRGHREYTESMCLLESELEAQLGEFHLRMKGLAGFARLCVGDQYEICMKYGRQRWK
  LRGRIEGSGKQVWDSEETIFLPLLTEFLSIKVTELKGLANHVVVGSVSCETKDLFAALPQ
  VVAVDINDLGTIKLSLEVTWSPFDKDDQPSAASSVNKASTVTKRFSTYSQSPPDTPSLRE
  QAFYNMLRRQEELENGTAWSLSSESSDDSSSPQLSGTARHSPAPRPLVQQPEPLPIQVAF
  RRPETPSSGPLDEEGAVAPVLANGHAPYSRTLSHISEASVDAALAEASVEAVGPESLAWG
  PSPPTHPAPTHGEHPSPVPPALDPGHSATSSTLGTTGSVPTSTDPAPSAHLDSVHKSTDS
  GPSELPGPTHTTTGSTYSAITTTHSAPSPLTHTTTGSTHKPIISTLTTTGPTLNIIGPVQ
  TTTSPTHTMPSPTHTTASPTHTSTSPTHTPTSPTHKTSMSPPTTTSPTPSGMGLVQTATS
  PTHPTTSPTHPTTSPILINVSPSTSLELATLSSPSKHSDPTLPGTDSLPCSPPVSNSYTQ
  ADPMAPRTPHPSPAHSSRKPLTSPAPDPSESTVQSLSPTPSPPTPAPQHSDLCLAMAVQT
  PVPTAAGGSGDRSLEEALGALMAALDDYRGQFPELQGLEQEVTRLESLLMQRQGLTRSRA
  SSLSITVEHALESFSFLNEDEDEDNDVPGDRPPSSPEAGAEDSIDSPSARPLSTGCPALD
  AALVRHLYHCSRLLLKLGTFGPLRCQEAWALERLLREARVLEAVCEFSRRWEIPASSAQE
  VVQFSASRPGFLTFWDQCTERLSCFLCPVERVLLTFCNQYGARLSLRQPGLAEAVCVKFL
  EDALGQKLPRRPQPGPGEQLTVFQFWSFVETLDSPTMEAYVTETAEEVLLVRNLNSDDQA
  VVLKALRLAPEGRLRRDGLRALSSLLVHGNNKVMAAVSTQLRSLSLGPTFRERALLCFLD
  QLEDEDVQTRVAGCLALGCIKAPEGIEPLVYLCQTDTEAVREAARQSLQQCGEEGQSAHR
  RLEESLDALPRIFGPGSMASTAF
• Function: Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration. Acts as an adapter protein, linking active Rho proteins to STK24 and STK26 kinases, and hence positively regulates Golgi reorientation in polarized cell migration upon Rho activation. Involved in the subcellular relocation of STK26 from the Golgi to cytoplasm punctae in a Rho- and PDCD10-dependent manner upon serum stimulation.

Molecular Interaction Atlas (MIA) of This DOT

9 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 Rho family-interacting cell polarization regulator 1 (RIPOR1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rho family-interacting cell polarization regulator 1 (RIPOR1).	[11]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] 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.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.