Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8TKE6F)

• DOT Name: G-protein coupled receptor 78 (GPR78)
• Gene Name: GPR78
• Related Disease:
  Bipolar disorder
  Lung squamous cell carcinoma
  Schizophrenia
  Lewy body dementia
  Lung cancer
  Lung carcinoma
  Neuroblastoma
  Parkinson disease
• UniProt ID: GPR78_HUMAN
• Pfam ID: PF00001
• Sequence:
  MGPGEALLAGLLVMVLAVALLSNALVLLCCAYSAELRTRASGVLLVNLSLGHLLLAALDM
  PFTLLGVMRGRTPSAPGACQVIGFLDTFLASNAALSVAALSADQWLAVGFPLRYAGRLRP
  RYAGLLLGCAWGQSLAFSGAALGCSWLGYSSAFASCSLRLPPEPERPRFAAFTATLHAVG
  FVLPLAVLCLTSLQVHRVARRHCQRMDTVTMKALALLADLHPSVRQRCLIQQKRRRHRAT
  RKIGIAIATFLICFAPYVMTRLAELVPFVTVNAQWGILSKCLTYSKAVADPFTYSLLRRP
  FRQVLAGMVHRLLKRTPRPASTHDSSLDVAGMVHQLLKRTPRPASTHNGSVDTENDSCLQ
  QTH
• Function: Orphan receptor. Displays a significant level of constitutive activity. Its effect is mediated by G(s)-alpha protein that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP.
• Tissue Specificity: High level of expression in placenta. Expressed throughout the brain at low level. No expression detected in skeletal muscle, lung, heart, liver, pancreas, or kidney.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bipolar disorder	DISAM7J2	Strong	Biomarker	[1]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[1]
Lewy body dementia	DISAE66J	Limited	Altered Expression	[3]
Lung cancer	DISCM4YA	Limited	Biomarker	[4]
Lung carcinoma	DISTR26C	Limited	Biomarker	[4]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[5]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of G-protein coupled receptor 78 (GPR78).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of G-protein coupled receptor 78 (GPR78).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of G-protein coupled receptor 78 (GPR78).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of G-protein coupled receptor 78 (GPR78).	[10]

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 G-protein coupled receptor 78 (GPR78).	[9]

References

• [1] Association analysis of the chromosome 4p-located G protein-coupled receptor 78 (GPR78) gene in bipolar affective disorder and schizophrenia.Mol Psychiatry. 2006 Apr;11(4):384-94. doi: 10.1038/sj.mp.4001786.
• [2] Predicting the Lung Squamous Cell Carcinoma Diagnosis and Prognosis Markers by Unique DNA Methylation and Gene Expression Profiles.J Comput Biol. 2020 Jul;27(7):1041-1054. doi: 10.1089/cmb.2019.0138. Epub 2019 Nov 11.
• [3] GRP78 Level Is Altered in the Brain, but Not in Plasma or Cerebrospinal Fluid in Parkinson's Disease Patients.Front Neurosci. 2019 Jul 5;13:697. doi: 10.3389/fnins.2019.00697. eCollection 2019.
• [4] GPR78 promotes lung cancer cell migration and metastasis by activation of Gq-Rho GTPase pathway.BMB Rep. 2016 Nov;49(11):623-628. doi: 10.5483/bmbrep.2016.49.11.133.
• [5] Common variants upstream of MLF1 at 3q25 and within CPZ at 4p16 associated with neuroblastoma.PLoS Genet. 2017 May 18;13(5):e1006787. doi: 10.1371/journal.pgen.1006787. eCollection 2017 May.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [9] 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.
• [10] 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.