Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4UMKUR)

• DOT Name: Calcineurin B homologous protein 2 (CHP2)
• Synonyms: Hepatocellular carcinoma-associated antigen 520
• Gene Name: CHP2
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Neoplasm
• UniProt ID: CHP2_HUMAN
• PDB ID: 2BEC
• Pfam ID: PF13202 ; PF13499
• Sequence:
  MGSRSSHAAVIPDGDSIRRETGFSQASLLRLHHRFRALDRNKKGYLSRMDLQQIGALAVN
  PLGDRIIESFFPDGSQRVDFPGFVRVLAHFRPVEDEDTETQDPKKPEPLNSRRNKLHYAF
  QLYDLDRDGKISRHEMLQVLRLMVGVQVTEEQLENIADRTVQEADEDGDGAVSFVEFTKS
  LEKMDVEQKMSIRILK
• Function: Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Binds to and activates SLC9A1/NHE1 in a serum-independent manner, thus increasing pH and protecting cells from serum deprivation-induced death. Also plays a role in the regulation of cell proliferation and tumor growth by increasing the phosphatase activity of PPP3CA in a calcium-dependent manner. Activator of the calcineurin/NFAT signaling pathway. Involved in the cytoplasmic translocation of the transcription factor NFATC3 to the nucleus.
• Tissue Specificity: Expressed in malignantly transformed cells but not detected in normal tissues.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	moderate	Biomarker	[3]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[3]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

6 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 Calcineurin B homologous protein 2 (CHP2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Calcineurin B homologous protein 2 (CHP2).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Calcineurin B homologous protein 2 (CHP2).	[7]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate decreases the expression of Calcineurin B homologous protein 2 (CHP2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Calcineurin B homologous protein 2 (CHP2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Calcineurin B homologous protein 2 (CHP2).	[11]

1 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 Calcineurin B homologous protein 2 (CHP2).	[10]

References

• [1] Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies.J Immunol. 2002 Jul 15;169(2):1102-9. doi: 10.4049/jimmunol.169.2.1102.
• [2] CHP2 Promotes Cell Proliferation in Breast Cancer via Suppression of FOXO3a.Mol Cancer Res. 2018 Oct;16(10):1512-1522. doi: 10.1158/1541-7786.MCR-18-0157. Epub 2018 Jul 2.
• [3] Overexpression of CHP2 enhances tumor cell growth, invasion and metastasis in ovarian cancer.In Vivo. 2007 Jul-Aug;21(4):593-8.
• [4] Quality control material for the detection of somatic mutations in fixed clinical specimens by next-generation sequencing.Diagn Pathol. 2015 Sep 17;10:169. doi: 10.1186/s13000-015-0403-0.
• [5] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [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] 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.