Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNSBH84)

• DOT Name: Cell cycle control protein 50B (TMEM30B)
• Synonyms: P4-ATPase flippase complex beta subunit TMEM30B; Transmembrane protein 30B
• Gene Name: TMEM30B
• Related Disease:
  Melanoma
  Meningioma
  Peritoneal mesothelioma
• UniProt ID: CC50B_HUMAN
• PDB ID: 7VGH
• Pfam ID: PF03381
• Sequence:
  MTWSATARGAHQPDNTAFTQQRLPAWQPLLSASIALPLFFCAGLAFIGLGLGLYYSSNGI
  KELEYDYTGDPGTGNCSVCAAAGQGRALPPPCSCAWYFSLPELFQGPVYLYYELTNFYQN
  NRRYGVSRDDAQLSGLPSALRHPVNECAPYQRSAAGLPIAPCGAIANSLFNDSFSLWHQR
  QPGGPYVEVPLDRSGIAWWTDYHVKFRNPPLVNGSLALAFQGTAPPPNWRRPVYELSPDP
  NNTGFINQDFVVWMRTAALPTFRKLYARIRQGNYSAGLPRGAYRVNITYNYPVRAFGGHK
  LLIFSSISWMGGKNPFLGIAYLVVGSLCILTGFVMLVVYIRYQDQDDDDEE
• Function: Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate (Probable). Can mediate the export of alpha subunits ATP8A1, ATP8B1, ATP8B2 and ATP8B4 from the ER to the plasma membrane.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanoma	DIS1RRCY	Strong	Biomarker	[1]
Meningioma	DISPT4TG	moderate	Genetic Variation	[2]
Peritoneal mesothelioma	DISW7W4V	Limited	Genetic Variation	[3]

15 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 Cell cycle control protein 50B (TMEM30B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cell cycle control protein 50B (TMEM30B).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cell cycle control protein 50B (TMEM30B).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cell cycle control protein 50B (TMEM30B).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cell cycle control protein 50B (TMEM30B).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cell cycle control protein 50B (TMEM30B).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cell cycle control protein 50B (TMEM30B).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cell cycle control protein 50B (TMEM30B).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cell cycle control protein 50B (TMEM30B).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cell cycle control protein 50B (TMEM30B).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Cell cycle control protein 50B (TMEM30B).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cell cycle control protein 50B (TMEM30B).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cell cycle control protein 50B (TMEM30B).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cell cycle control protein 50B (TMEM30B).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cell cycle control protein 50B (TMEM30B).	[16]

References

• [1] Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.Cancer Res. 2006 Jun 15;66(12):6080-6. doi: 10.1158/0008-5472.CAN-06-0157.
• [2] Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas.Neuro Oncol. 2010 Dec;12(12):1278-90. doi: 10.1093/neuonc/noq081. Epub 2010 Aug 4.
• [3] Characterization of DNA hypermethylation in two cases of peritoneal mesothelioma.Tumour Biol. 2012 Dec;33(6):2031-40. doi: 10.1007/s13277-012-0462-8. Epub 2012 Jul 27.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] Profile of estrogen-responsive genes in an estrogen-specific mammary gland outgrowth model. Mol Reprod Dev. 2009 Aug;76(8):733-50. doi: 10.1002/mrd.21041.
• [9] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] 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.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.