Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCIMJ8E)

• DOT Name: Carbonic anhydrase 5B, mitochondrial (CA5B)
• Synonyms: EC 4.2.1.1; Carbonate dehydratase VB; Carbonic anhydrase VB; CA-VB
• Gene Name: CA5B
• UniProt ID: CAH5B_HUMAN
• EC Number: 4.2.1.1
• Pfam ID: PF00194
• Sequence:
  MVVMNSLRVILQASPGKLLWRKFQIPRFMPARPCSLYTCTYKTRNRALHPLWESVDLVPG
  GDRQSPINIRWRDSVYDPGLKPLTISYDPATCLHVWNNGYSFLVEFEDSTDKSVIKGGPL
  EHNYRLKQFHFHWGAIDAWGSEHTVDSKCFPAELHLVHWNAVRFENFEDAALEENGLAVI
  GVFLKLGKHHKELQKLVDTLPSIKHKDALVEFGSFDPSCLMPTCPDYWTYSGSLTTPPLS
  ESVTWIIKKQPVEVDHDQLEQFRTLLFTSEGEKEKRMVDNFRPLQPLMNRTVRSSFRHDY
  VLNVQAKPKPATSQATP
• Function: Mitochondrial carbonic anhydrase that catalyzes the reversible conversion of carbon dioxide to bicarbonate/HCO3.
• Tissue Specificity: Strongest expression in heart, pancreas, kidney, placenta, lung, and skeletal muscle. Not expressed in liver.
• KEGG Pathway:
  Nitrogen metabolism (hsa00910)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Reversible hydration of carbon dioxide (R-HSA-1475029)

Molecular Interaction Atlas (MIA) of This DOT

8 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 Carbonic anhydrase 5B, mitochondrial (CA5B).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[8]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Carbonic anhydrase 5B, mitochondrial (CA5B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Carbonic anhydrase 5B, mitochondrial (CA5B).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Carbonic anhydrase 5B, mitochondrial (CA5B).	[7]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] 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.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [10] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.