Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWWM6HI)

• DOT Name: Calcium homeostasis modulator protein 2 (CALHM2)
• Synonyms: Protein FAM26B
• Gene Name: CALHM2
• UniProt ID: CAHM2_HUMAN
• PDB ID: 6LMU; 6LMW; 6LMX; 6UIV; 6UIW; 6UIX; 6VAI; 6VAK; 6VAL
• Pfam ID: PF14798
• Sequence:
  MAALIAENFRFLSLFFKSKDVMIFNGLVALGTVGSQELFSVVAFHCPCSPARNYLYGLAA
  IGVPALVLFIIGIILNNHTWNLVAECQHRRTKNCSAAPTFLLLSSILGRAAVAPVTWSVI
  SLLRGEAYVCALSEFVDPSSLTAREEHFPSAHATEILARFPCKENPDNLSDFREEVSRRL
  RYESQLFGWLLIGVVAILVFLTKCLKHYCSPLSYRQEAYWAQYRANEDQLFQRTAEVHSR
  VLAANNVRRFFGFVALNKDDEELIANFPVEGTQPRPQWNAITGVYLYRENQGLPLYSRLH
  KWAQGLAGNGAAPDNVEMALLPS
• Function: Pore-forming subunit of a voltage-gated ion channel.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[8]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Calcium homeostasis modulator protein 2 (CALHM2).	[13]

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 Calcium homeostasis modulator protein 2 (CALHM2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcium homeostasis modulator protein 2 (CALHM2).	[10]

References

• [1] 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.
• [2] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] CRISPR-based DNA methylation editing of NNT rescues the cisplatin resistance of lung cancer cells by reducing autophagy. Arch Toxicol. 2023 Feb;97(2):441-456. doi: 10.1007/s00204-022-03404-0. Epub 2022 Nov 6.
• [10] 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.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.