Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDB4FM2)

• DOT Name: RIB43A-like with coiled-coils protein 2 (RIBC2)
• Gene Name: RIBC2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Ulcerative colitis
• UniProt ID: RIBC2_HUMAN
• PDB ID: 7UNG; 8J07
• Pfam ID: PF05914
• Sequence:
  MGSQTMAVALPRDLRQDANLAKRRHAELCRQKRVFNARNRIIGGDTEAWDVQVHDQKIKE
  ATEKARHETFAAEMRQNDKIMCILENRKKRDRKNLCRAINDFQQSFQKPETRREFDLSDP
  LALKKDLPARQSDNDVRNTISGMQKFMGEDLNFHERKKFQEEQNREWSLQQQREWKNARA
  EQKCAEALYTETRLQFDETAKHLQKLESTTRKAVCASVKDFNKSQAIESVERKKQEKKQE
  QEDNLAEITNLLRGDLLSENPQQAASSFGPHRVVPDRWKGMTQEQLEQIRLVQKQQIQEK
  LRLQEEKRQRDLDWDRRRIQGARATLLFERQQWRRQRDLRRALDSSNLSLAKEQHLQKKY
  MNEVYTNQPTGDYFTQFNTGSR
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
• Tissue Specificity: Expressed in airway epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Ulcerative colitis	DIS8K27O	Strong	Posttranslational Modification	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of RIB43A-like with coiled-coils protein 2 (RIBC2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RIB43A-like with coiled-coils protein 2 (RIBC2).	[10]

References

• [1] Pseudokinases: a tribble-edged sword.FEBS J. 2020 Oct;287(19):4170-4182. doi: 10.1111/febs.15096. Epub 2019 Oct 31.
• [2] An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells. Cancer Sci. 2011 Jul;102(7):1410-7. doi: 10.1111/j.1349-7006.2011.01948.x. Epub 2011 May 5.
• [3] A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis.Int J Mol Sci. 2016 Aug 9;17(8):1291. doi: 10.3390/ijms17081291.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] 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.
• [11] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent. Toxicology. 2010 Apr 11;270(2-3):137-49. doi: 10.1016/j.tox.2010.02.008. Epub 2010 Feb 17.