Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTERUPP6)

• DOT Name: Neuron-specific calcium-binding protein hippocalcin (HPCA)
• Synonyms: Calcium-binding protein BDR-2
• Gene Name: HPCA
• Related Disease:
  Alzheimer disease
  Colorectal carcinoma
  Dystonia
  Huntington disease
  Neoplasm
  Severe combined immunodeficiency
  Torsion dystonia 2
• UniProt ID: HPCA_HUMAN
• PDB ID: 5G4P; 5G58; 5M6C; 7OWM
• Pfam ID: PF00036 ; PF13499
• Sequence:
  MGKQNSKLRPEMLQDLRENTEFSELELQEWYKGFLKDCPTGILNVDEFKKIYANFFPYGD
  ASKFAEHVFRTFDTNSDGTIDFREFIIALSVTSRGRLEQKLMWAFSMYDLDGNGYISREE
  MLEIVQAIYKMVSSVMKMPEDESTPEKRTEKIFRQMDTNNDGKLSLEEFIRGAKSDPSIV
  RLLQCDPSSASQF
• Function: Calcium-binding protein that may play a role in the regulation of voltage-dependent calcium channels. May also play a role in cyclic-nucleotide-mediated signaling through the regulation of adenylate and guanylate cyclases.
• Tissue Specificity: Brain specific.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Dystonia	DISJLFGW	Strong	Genetic Variation	[3]
Huntington disease	DISQPLA4	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[5]
Torsion dystonia 2	DIS9RSUT	Strong	Autosomal recessive	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neuron-specific calcium-binding protein hippocalcin (HPCA).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neuron-specific calcium-binding protein hippocalcin (HPCA).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Neuron-specific calcium-binding protein hippocalcin (HPCA).	[9]

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 Neuron-specific calcium-binding protein hippocalcin (HPCA).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Neuron-specific calcium-binding protein hippocalcin (HPCA).	[11]

References

• [1] Role of hippocalcin in mediating A toxicity.Biochim Biophys Acta. 2012 Aug;1822(8):1247-57. doi: 10.1016/j.bbadis.2012.04.007. Epub 2012 Apr 20.
• [2] Expression profiling shows differential molecular pathways and provides potential new diagnostic biomarkers for colorectal serrated adenocarcinoma.Int J Cancer. 2013 Jan 15;132(2):297-307. doi: 10.1002/ijc.27674. Epub 2012 Jun 28.
• [3] Perturbed Ca(2+)-dependent signaling of DYT2 hippocalcin mutant as mechanism of autosomal recessive dystonia.Neurobiol Dis. 2019 Dec;132:104529. doi: 10.1016/j.nbd.2019.104529. Epub 2019 Jul 10.
• [4] Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons.J Neurochem. 2009 Oct;111(2):460-72. doi: 10.1111/j.1471-4159.2009.06344.x. Epub 2009 Aug 17.
• [5] Role of interleukin 10 and transforming growth factor beta1 in the angiogenesis and metastasis of human prostate primary tumor lines from orthotopic implants in severe combined immunodeficiency mice.Clin Cancer Res. 1999 Mar;5(3):711-20.
• [6] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [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] 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.