Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL5INE4)

• DOT Name: EF-hand domain-containing protein D1 (EFHD1)
• Synonyms: EF-hand domain-containing protein 1; Swiprosin-2
• Gene Name: EFHD1
• Related Disease: Colorectal carcinoma
• UniProt ID: EFHD1_HUMAN
• Pfam ID: PF13499
• Sequence:
  MASEELACKLERRLRREEAEESGPQLAPLGAPAPEPKPEPEPPARAPTASADAELSAQLS
  RRLDINEGAARPRRCRVFNPYTEFPEFSRRLIKDLESMFKLYDAGRDGFIDLMELKLMME
  KLGAPQTHLGLKSMIKEVDEDFDGKLSFREFLLIFHKAAAGELQEDSGLMALAKLSEIDV
  ALEGVKGAKNFFEAKVQALSSASKFEAELKAEQDERKREEEERRLRQAAFQKLKANFNT
• Function: Acts as a calcium sensor for mitochondrial flash (mitoflash) activation, an event characterized by stochastic bursts of superoxide production. May play a role in neuronal differentiation.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	EF-hand domain-containing protein D1 (EFHD1) affects the response to substance of Fluorouracil.	[20]

16 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 EF-hand domain-containing protein D1 (EFHD1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of EF-hand domain-containing protein D1 (EFHD1).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of EF-hand domain-containing protein D1 (EFHD1).	[7]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of EF-hand domain-containing protein D1 (EFHD1).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of EF-hand domain-containing protein D1 (EFHD1).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of EF-hand domain-containing protein D1 (EFHD1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of EF-hand domain-containing protein D1 (EFHD1).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of EF-hand domain-containing protein D1 (EFHD1).	[18]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of EF-hand domain-containing protein D1 (EFHD1).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of EF-hand domain-containing protein D1 (EFHD1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of EF-hand domain-containing protein D1 (EFHD1).	[15]

References

• [1] Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients.Cancer Med. 2014 Oct;3(5):1235-45. doi: 10.1002/cam4.273. Epub 2014 May 24.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [8] 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.
• [9] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [10] 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.
• [11] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [12] 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.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [14] 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.
• [15] 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.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [19] Cordycepin inhibits the proliferation and progression of NPC by targeting the MAPK/ERK and -catenin pathways. Oncol Lett. 2022 Jan;23(1):20. doi: 10.3892/ol.2021.13138. Epub 2021 Nov 16.
• [20] 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.