Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ9QV3U)

• DOT Name: Large ribosomal subunit protein bL36m (MRPL36)
• Synonyms: 39S ribosomal protein L36, mitochondrial; L36mt; MRP-L36; BRCA1-interacting protein 1
• Gene Name: MRPL36
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Colon carcinoma
  Fanconi's anemia
  Nijmegen breakage syndrome
• UniProt ID: RM36_HUMAN
• PDB ID: 3J7Y ; 3J9M ; 5OOL ; 6I9R ; 6NU2 ; 6NU3 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5I ; 7A5J ; 7A5K ; 7L08 ; 7L20 ; 7O9K ; 7O9M ; 7ODR ; 7ODS ; 7ODT ; 7OF0 ; 7OF2 ; 7OF3 ; 7OF4 ; 7OF5 ; 7OF6 ; 7OF7 ; 7OG4 ; 7OIC ; 7OID ; 7OIE ; 7PD3 ; 7QH7 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8OIR ; 8OIT
• Pfam ID: PF00444
• Sequence:
  MANLFIRKMVNPLLYLSRHTVKPRALSTFLFGSIRGAAPVAVEPGAAVRSLLSPGLLPHL
  LPALGFKNKTVLKKRCKDCYLVKRRGRWYVYCKTHPRHKQRQM
• KEGG Pathway: Ribosome (hsa03010)
• Reactome Pathway:
  Mitochondrial translation elongation (R-HSA-5389840)
  Mitochondrial translation termination (R-HSA-5419276)
  Mitochondrial translation initiation (R-HSA-5368286)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Genetic Variation	[4]
Colon carcinoma	DISJYKUO	Strong	Genetic Variation	[4]
Fanconi's anemia	DISGW6Q8	Strong	Genetic Variation	[5]
Nijmegen breakage syndrome	DIS98HVL	Strong	Genetic Variation	[2]

1 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 Large ribosomal subunit protein bL36m (MRPL36).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Large ribosomal subunit protein bL36m (MRPL36).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein bL36m (MRPL36).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Large ribosomal subunit protein bL36m (MRPL36).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Large ribosomal subunit protein bL36m (MRPL36).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Large ribosomal subunit protein bL36m (MRPL36).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Large ribosomal subunit protein bL36m (MRPL36).	[12]

References

• [1] Four common polymorphisms of BRIP1 (rs2048718, rs4988344, rs4986764, and rs6504074) and cancer risk: evidence from 13,716 cancer patients and 15,590 cancer-free controls.Aging (Albany NY). 2018 Feb 16;10(2):266-277. doi: 10.18632/aging.101388.
• [2] Association of Single-Nucleotide Polymorphisms in Monoubiquitinated FANCD2-DNA Damage Repair Pathway Genes With Breast Cancer in the Chinese Population.Technol Cancer Res Treat. 2018 Jan 1;17:1533033818819841. doi: 10.1177/1533033818819841.
• [3] MicroRNA-543 acts as a prognostic marker and promotes the cell proliferation in cervical cancer by BRCA1-interacting protein 1.Tumour Biol. 2017 Feb;39(2):1010428317691187. doi: 10.1177/1010428317691187.
• [4] BRIP-1 germline mutation and its role in colon cancer: presentation of two case reports and review of literature.BMC Med Genet. 2019 May 7;20(1):75. doi: 10.1186/s12881-019-0812-0.
• [5] BRIP1 (BACH1) variants and familial breast cancer risk: a case-control study.BMC Cancer. 2007 May 15;7:83. doi: 10.1186/1471-2407-7-83.
• [6] 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.
• [7] Human 3D multicellular microtissues: an upgraded model for the in vitro mechanistic investigation of inflammation-associated drug toxicity. Toxicol Lett. 2019 Sep 15;312:34-44.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.