Details of Drug Off-Target (DOT)

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

• DOT Name: Hippocalcin-like protein 1 (HPCAL1)
• Synonyms: Calcium-binding protein BDR-1; HLP2; Visinin-like protein 3; VILIP-3
• Gene Name: HPCAL1
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  High blood pressure
  Advanced cancer
  Central hypoventilation syndrome, congenital
  Neuroblastoma
  Hepatitis C virus infection
  Hepatocellular carcinoma
• UniProt ID: HPCL1_HUMAN
• PDB ID: 5T7C
• Pfam ID: PF13499
• Sequence:
  MGKQNSKLRPEVLQDLRENTEFTDHELQEWYKGFLKDCPTGHLTVDEFKKIYANFFPYGD
  ASKFAEHVFRTFDTNGDGTIDFREFIIALSVTSRGKLEQKLKWAFSMYDLDGNGYISRSE
  MLEIVQAIYKMVSSVMKMPEDESTPEKRTDKIFRQMDTNNDGKLSLEEFIRGAKSDPSIV
  RLLQCDPSSASQF
• Function: May be involved in the calcium-dependent regulation of rhodopsin phosphorylation.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
High blood pressure	DISY2OHH	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[3]
Central hypoventilation syndrome, congenital	DISQRK53	moderate	Genetic Variation	[3]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[3]
Hepatitis C virus infection	DISQ0M8R	Limited	Altered Expression	[4]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[4]

19 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 Hippocalcin-like protein 1 (HPCAL1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Hippocalcin-like protein 1 (HPCAL1).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[15]
Selenium	DM25CGV	Approved	Selenium increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[16]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[17]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[18]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Hippocalcin-like protein 1 (HPCAL1).	[19]
Desloratadine	DM56YN7	Approved	Desloratadine decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[20]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Hippocalcin-like protein 1 (HPCAL1).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Hippocalcin-like protein 1 (HPCAL1).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Hippocalcin-like protein 1 (HPCAL1).	[24]

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 Hippocalcin-like protein 1 (HPCAL1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Hippocalcin-like protein 1 (HPCAL1).	[22]

References

• [1] HPCAL1 promotes glioblastoma proliferation via activation of Wnt/-catenin signalling pathway.J Cell Mol Med. 2019 May;23(5):3108-3117. doi: 10.1111/jcmm.14083. Epub 2019 Mar 6.
• [2] Hypertension susceptibility genes on chromosome 2p24-p25 in a general Japanese population.J Hypertens. 2005 May;23(5):955-60. doi: 10.1097/01.hjh.0000166835.70935.3c.
• [3] Mutations that disrupt PHOXB interaction with the neuronal calcium sensor HPCAL1 impede cellular differentiation in neuroblastoma.Oncogene. 2014 Jun 19;33(25):3316-24. doi: 10.1038/onc.2013.290. Epub 2013 Jul 22.
• [4] Hepatitis C virus core impacts expression of miR122 and miR204 involved in carcinogenic progression via regulation of TGFBRAP1 and HOTTIP expression.Onco Targets Ther. 2018 Mar 2;11:1173-1182. doi: 10.2147/OTT.S149254. eCollection 2018.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [11] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] 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.
• [14] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [15] Proteomic analysis of liver cancer cells treated with suberonylanilide hydroxamic acid. Cancer Chemother Pharmacol. 2008 Apr;61(5):791-802.
• [16] 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.
• [17] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [18] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [19] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [20] Blockade of NMT1 enzymatic activity inhibits N-myristoylation of VILIP3 protein and suppresses liver cancer progression. Signal Transduct Target Ther. 2023 Jan 9;8(1):14. doi: 10.1038/s41392-022-01248-9.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] 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.
• [23] 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.
• [24] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.