Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT6Z3XS)

• DOT Name: Carbonic anhydrase 13 (CA13)
• Synonyms: EC 4.2.1.1; Carbonate dehydratase XIII; Carbonic anhydrase XIII; CA-XIII
• Gene Name: CA13
• UniProt ID: CAH13_HUMAN
• PDB ID: 3CZV; 3D0N; 3DA2; 4HU1; 4KNM; 4KNN; 4QIZ; 4QJP; 4QJX; 4QSJ; 5E2N; 5LLA; 5LLN; 5OGJ; 5OHH; 6G5U
• EC Number: 4.2.1.1
• Pfam ID: PF00194
• Sequence:
  MSRLSWGYREHNGPIHWKEFFPIADGDQQSPIEIKTKEVKYDSSLRPLSIKYDPSSAKII
  SNSGHSFNVDFDDTENKSVLRGGPLTGSYRLRQVHLHWGSADDHGSEHIVDGVSYAAELH
  VVHWNSDKYPSFVEAAHEPDGLAVLGVFLQIGEPNSQLQKITDTLDSIKEKGKQTRFTNF
  DLLSLLPPSWDYWTYPGSLTVPPLLESVTWIVLKQPINISSQQLAKFRSLLCTAEGEAAA
  FLVSNHRPPQPLKGRKVRASFH
• Function: Reversible hydration of carbon dioxide.
• Tissue Specificity: Expressed in thymus, small intestine, spleen, prostate, ovary, colon and testis.
• 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 13 (CA13).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Carbonic anhydrase 13 (CA13).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carbonic anhydrase 13 (CA13).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Carbonic anhydrase 13 (CA13).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Carbonic anhydrase 13 (CA13).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Carbonic anhydrase 13 (CA13).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Carbonic anhydrase 13 (CA13).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Carbonic anhydrase 13 (CA13).	[11]

3 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 13 (CA13).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Carbonic anhydrase 13 (CA13).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Carbonic anhydrase 13 (CA13).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [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] 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.
• [6] 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.
• [7] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [8] 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.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.