Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTESJ6JD)

• DOT Name: Alpha-catulin (CTNNAL1)
• Synonyms: Alpha-catenin-related protein; ACRP; Catenin alpha-like protein 1
• Gene Name: CTNNAL1
• Related Disease:
  Advanced cancer
  Epithelial ovarian cancer
  Head-neck squamous cell carcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Riley-Day syndrome
  Squamous cell carcinoma
  Melanoma
• UniProt ID: CTNL1_HUMAN
• Pfam ID: PF01044
• Sequence:
  MAASPGPAGVGGAGAVYGSGSSGFALDSGLEIKTRSVEQTLLPLVSQITTLINHKDNTKK
  SDKTLQAIQRVGQAVNLAVGRFVKVGEAIANENWDLKEEINIACIEAKQAGETIAALTDI
  TNLNHLESDGQITIFTDKTGVIKAARLLLSSVTKVLLLADRVVIKQIITSRNKVLATMER
  LEKVNSFQEFVQIFSQFGNEMVEFAHLSGDRQNDLKDEKKKAKMAAARAVLEKCTMMLLT
  ASKTCLRHPNCESAHKNKEGVFDRMKVALDKVIEIVTDCKPNGETDISSISIFTGIKEFK
  MNIEALRENLYFQSKENLSVTLEVILERMEDFTDSAYTSHEHRERILELSTQARMELQQL
  ISVWIQAQSKKTKSIAEELELSILKISHSLNELKKELHSTATQLAADLLKYHADHVVLKA
  LKLTGVEGNLEALAEYACKLSEQKEQLVETCRLLRHISGTEPLEITCIHAEETFQVTGQQ
  IISAAETLTLHPSSKIAKENLDVFCEAWESQISDMSTLLREINDVFEGRRGEKYGYLSLP
  KPMKNNANLKSLKPDKPDSEEQAKIAKLGLKLGLLTSDADCEIEKWEDQENEIVQYGRNM
  SSMAYSLYLFTRGEGPLKTSQDLIHQLEVFAAEGLKLTSSVQAFSKQLKDDDKLMLLLEI
  NKLIPLCHQLQTVTKTSLQNKVFLKVDKCITKTRSMMALLVQLLSLCYKLLKKLQMENNG
  WVSVTNKDTMDSKT
• Function: May modulate the Rho pathway signaling by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor (ARHGEF1).
• Tissue Specificity: Widely expressed. Expressed at lower level in neural tissues and at the highest level in the adrenal gland.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[2]
Riley-Day syndrome	DISJZHNP	Strong	Biomarker	[3]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[1]
Melanoma	DIS1RRCY	moderate	Altered Expression	[4]

21 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 Alpha-catulin (CTNNAL1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Alpha-catulin (CTNNAL1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alpha-catulin (CTNNAL1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Alpha-catulin (CTNNAL1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Alpha-catulin (CTNNAL1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Alpha-catulin (CTNNAL1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Alpha-catulin (CTNNAL1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Alpha-catulin (CTNNAL1).	[12]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Alpha-catulin (CTNNAL1).	[13]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Alpha-catulin (CTNNAL1).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Alpha-catulin (CTNNAL1).	[16]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Alpha-catulin (CTNNAL1).	[17]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Alpha-catulin (CTNNAL1).	[18]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Alpha-catulin (CTNNAL1).	[19]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Alpha-catulin (CTNNAL1).	[20]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Alpha-catulin (CTNNAL1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Alpha-catulin (CTNNAL1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-catulin (CTNNAL1).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Alpha-catulin (CTNNAL1).	[24]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Alpha-catulin (CTNNAL1).	[25]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Alpha-catulin (CTNNAL1).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Alpha-catulin (CTNNAL1).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Alpha-catulin (CTNNAL1).	[22]

References

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• [2] Amazon Fruits Inhibit Growth and Promote Pro-apoptotic Effects on Human Ovarian Carcinoma Cell Lines.Biomolecules. 2019 Nov 6;9(11):707. doi: 10.3390/biom9110707.
• [3] Alpha-catulin maps to the familial dysautonomia region on 9q31.Genome. 2001 Dec;44(6):990-4. doi: 10.1139/g01-103.
• [4] Alpha-catulin contributes to drug-resistance of melanoma by activating NF-B and AP-1.PLoS One. 2015 Mar 20;10(3):e0119402. doi: 10.1371/journal.pone.0119402. eCollection 2015.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] 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.
• [7] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [8] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] 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.
• [12] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [13] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [14] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [18] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [19] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [20] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [21] 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.
• [22] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [23] 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.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [25] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [26] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.