Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM8COM5)

• DOT Name: Ran-binding protein 9 (RANBP9)
• Synonyms: RanBP9; BPM-L; BPM90; Ran-binding protein M; RanBPM; RanBP7
• Gene Name: RANBP9
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Ataxia-telangiectasia
  Autism
  Breast neoplasm
  Non-small-cell lung cancer
  Tauopathy
  Gastric cancer
  Metastatic malignant neoplasm
  Neoplasm
  Stomach cancer
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Lung cancer
  Lung carcinoma
  Osteosarcoma
  Schizophrenia
• UniProt ID: RANB9_HUMAN
• PDB ID: 5JI7; 5JI9; 5JIU; 7NSC
• Pfam ID: PF10607 ; PF08513 ; PF00622
• Sequence:
  MSGQPPPPPPQQQQQQQQLSPPPPAALAPVSGVVLPAPPAVSAGSSPAGSPGGGAGGEGL
  GAAAAALLLHPPPPPPPATAAPPPPPPPPPPPASAAAPASGPPAPPGLAAGPGPAGGAPT
  PALVAGSSAAAPFPHGDSALNEQEKELQRRLKRLYPAVDEQETPLPRSWSPKDKFSYIGL
  SQNNLRVHYKGHGKTPKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVN
  MNRLPGWDKHSYGYHGDDGHSFCSSGTGQPYGPTFTTGDVIGCCVNLINNTCFYTKNGHS
  LGIAFTDLPPNLYPTVGLQTPGEVVDANFGQHPFVFDIEDYMREWRTKIQAQIDRFPIGD
  REGEWQTMIQKMVSSYLVHHGYCATAEAFARSTDQTVLEELASIKNRQRIQKLVLAGRMG
  EAIETTQQLYPSLLERNPNLLFTLKVRQFIEMVNGTDSEVRCLGGRSPKSQDSYPVSPRP
  FSSPSMSPSHGMNIHNLASGKGSTAHFSGFESCSNGVISNKAHQSYCHSNKHQSSNLNVP
  ELNSINMSRSQQVNNFTSNDVDMETDHYSNGVGETSSNGFLNGSSKHDHEMEDCDTEMEV
  DSSQLRRQLCGGSQAAIERMIHFGRELQAMSEQLRRDCGKNTANKKMLKDAFSLLAYSDP
  WNSPVGNQLDPIQREPVCSALNSAILETHNLPKQPPLALAMGQATQCLGLMARSGIGSCA
  FATVEDYLH
• Function: May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Acts as a mediator of cell spreading and actin cytoskeleton rearrangement. Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA.
• Tissue Specificity: Ubiquitously expressed, with highest levels in testes, placenta, heart, and muscle, and lowest levels in lung. Within the brain, expressed predominantly by neurons in the gray matter of cortex, the granular layer of cerebellum and the Purkinje cells.
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  MET activates RAS signaling (R-HSA-8851805)
  L1CAM interactions (R-HSA-373760)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[3]
Autism	DISV4V1Z	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Tauopathy	DISY2IPA	Strong	Genetic Variation	[2]
Gastric cancer	DISXGOUK	moderate	Biomarker	[7]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[7]
Neoplasm	DISZKGEW	moderate	Biomarker	[8]
Stomach cancer	DISKIJSX	moderate	Biomarker	[7]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[9]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[9]
Lung cancer	DISCM4YA	Limited	Biomarker	[11]
Lung carcinoma	DISTR26C	Limited	Biomarker	[11]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[9]
Schizophrenia	DISSRV2N	Limited	Biomarker	[4]

12 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 Ran-binding protein 9 (RANBP9).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ran-binding protein 9 (RANBP9).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ran-binding protein 9 (RANBP9).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ran-binding protein 9 (RANBP9).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ran-binding protein 9 (RANBP9).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ran-binding protein 9 (RANBP9).	[17]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ran-binding protein 9 (RANBP9).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ran-binding protein 9 (RANBP9).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ran-binding protein 9 (RANBP9).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ran-binding protein 9 (RANBP9).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ran-binding protein 9 (RANBP9).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ran-binding protein 9 (RANBP9).	[22]

2 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 affects the phosphorylation of Ran-binding protein 9 (RANBP9).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Ran-binding protein 9 (RANBP9).	[20]

References

• [1] Cell signalling pathway regulation by RanBPM: molecular insights and disease implications.Open Biol. 2017 Jun;7(6):170081. doi: 10.1098/rsob.170081.
• [2] Enhanced tau pathology via RanBP9 and Hsp90/Hsc70 chaperone complexes.Hum Mol Genet. 2017 Oct 15;26(20):3973-3988. doi: 10.1093/hmg/ddx284.
• [3] Scorpins in the DNA Damage Response.Int J Mol Sci. 2018 Jun 17;19(6):1794. doi: 10.3390/ijms19061794.
• [4] Mind Bomb-Binding Partner RanBP9 Plays a Contributory Role in Retinal Development.Mol Cells. 2017 Apr;40(4):271-279. doi: 10.14348/molcells.2017.2308. Epub 2017 Mar 28.
• [5] RanBPM interacts with psoriasin in vitro and their expression correlates with specific clinical features in vivo in breast cancer.BMC Cancer. 2002 Nov 6;2:28. doi: 10.1186/1471-2407-2-28.
• [6] RANBP9 affects cancer cells response to genotoxic stress and its overexpression is associated with worse response to platinum in NSCLC patients.Oncogene. 2018 Dec;37(50):6463-6476. doi: 10.1038/s41388-018-0424-8. Epub 2018 Aug 3.
• [7] Reduced RanBPM Expression Is Associated with Distant Metastasis in Gastric Cancer and Chemoresistance.Anticancer Res. 2016 Mar;36(3):1295-303.
• [8] Regulation of c-Raf Stability through the CTLH Complex.Int J Mol Sci. 2019 Feb 21;20(4):934. doi: 10.3390/ijms20040934.
• [9] RANBP9 suppresses tumor proliferation in colorectal cancer.Oncol Lett. 2019 May;17(5):4409-4416. doi: 10.3892/ol.2019.10134. Epub 2019 Mar 8.
• [10] RanBPM inhibits BLT2-mediated IL-8 production and invasiveness in aggressive breast cancer cells.Biochem Biophys Res Commun. 2017 Jan 29;483(1):305-311. doi: 10.1016/j.bbrc.2016.12.147. Epub 2016 Dec 25.
• [11] Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells.Oncotarget. 2016 Apr 5;7(14):18371-83. doi: 10.18632/oncotarget.7813.
• [12] 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.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [16] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [17] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [18] 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.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] 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.
• [21] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.