Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB2QZDY)

• DOT Name: Large ribosomal subunit protein mL40 (MRPL40)
• Synonyms: 39S ribosomal protein L40, mitochondrial; L40mt; MRP-L40; Nuclear localization signal-containing protein deleted in velocardiofacial syndrome; Up-regulated in metastasis
• Gene Name: MRPL40
• Related Disease:
  Breast carcinoma
  Melanoma
  Metastatic malignant neoplasm
  Velocardiofacial syndrome
  Neoplasm
• UniProt ID: RM40_HUMAN
• PDB ID: 3J7Y ; 3J9M ; 5OOL ; 5OOM ; 6I9R ; 6NU2 ; 6NU3 ; 6VLZ ; 6VMI ; 6ZM5 ; 6ZM6 ; 6ZS9 ; 6ZSA ; 6ZSB ; 6ZSC ; 6ZSD ; 6ZSE ; 6ZSG ; 7A5F ; 7A5G ; 7A5H ; 7A5I ; 7A5J ; 7A5K ; 7L08 ; 7L20 ; 7O9K ; 7O9M ; 7ODR ; 7ODS ; 7ODT ; 7OF0 ; 7OF2 ; 7OF3 ; 7OF4 ; 7OF5 ; 7OF6 ; 7OF7 ; 7OG4 ; 7OI7 ; 7OI8 ; 7OI9 ; 7OIA ; 7OIB ; 7OIC ; 7OID ; 7OIE ; 7PD3 ; 7PO4 ; 7QI4 ; 7QI5 ; 7QI6 ; 8ANY ; 8OIR ; 8OIT
• Pfam ID: PF09812
• Sequence:
  MTASVLRSISLALRPTSGLLGTWQTQLRETHQRASLLSFWELIPMRSEPLRKKKKVDPKK
  DQEAKERLKRKIRKLEKATQELIPIEDFITPLKFLDKARERPQVELTFEETERRALLLKK
  WSLYKQQERKMERDTIRAMLEAQQEALEELQLESPKLHAEAIKRDPNLFPFEKEGPHYTP
  PIPNYQPPEGRYNDITKVYTQVEFKR
• Tissue Specificity: Ubiquitous.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Melanoma	DIS1RRCY	Strong	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[1]
Velocardiofacial syndrome	DISOSBTY	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Large ribosomal subunit protein mL40 (MRPL40) affects the response to substance of Paclitaxel.	[10]

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 mL40 (MRPL40).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Large ribosomal subunit protein mL40 (MRPL40).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Large ribosomal subunit protein mL40 (MRPL40).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Large ribosomal subunit protein mL40 (MRPL40).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Large ribosomal subunit protein mL40 (MRPL40).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Large ribosomal subunit protein mL40 (MRPL40).	[9]

References

• [1] Identification of URIM, a novel gene up-regulated in metastasis.Anticancer Res. 1999 Jan-Feb;19(1A):525-30.
• [2] Isolation and characterization of a human gene containing a nuclear localization signal from the critical region for velo-cardio-facial syndrome on 22q11.Genomics. 1998 Oct 15;53(2):146-54. doi: 10.1006/geno.1998.5488.
• [3] Transcriptional profiling of human mammary carcinoma cell lines reveals PKW, a new tumor-specific gene.Anticancer Res. 2000 Jul-Aug;20(4):2255-64.
• [4] 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.
• [5] 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.
• [6] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [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] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.