Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFTH6ZY)

• DOT Name: Golgi-associated plant pathogenesis-related protein 1 (GLIPR2)
• Synonyms: GAPR-1; Golgi-associated PR-1 protein; Glioma pathogenesis-related protein 2; GliPR 2
• Gene Name: GLIPR2
• Related Disease:
  Diabetic kidney disease
  Glioma
  Hepatocellular carcinoma
  Renal fibrosis
• UniProt ID: GAPR1_HUMAN
• PDB ID: 1SMB; 4AIW; 5VHG
• Pfam ID: PF00188
• Sequence:
  MGKSASKQFHNEVLKAHNEYRQKHGVPPLKLCKNLNREAQQYSEALASTRILKHSPESSR
  GQCGENLAWASYDQTGKEVADRWYSEIKNYNFQQPGFTSGTGHFTAMVWKNTKKMGVGKA
  SASDGSSFVVARYFPAGNVVNEGFFEENVLPPKK
• Tissue Specificity: Highest expression in lung and peripheral leukocytes, and minor expression in liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[9]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Golgi-associated plant pathogenesis-related protein 1 (GLIPR2).	[15]

References

• [1] GLIPR-2 overexpression in HK-2 cells promotes cell EMT and migration through ERK1/2 activation.PLoS One. 2013;8(3):e58574. doi: 10.1371/journal.pone.0058574. Epub 2013 Mar 13.
• [2] Hypoxia promotes epithelial--mesenchymal transition of hepatocellular carcinoma cells via inducing GLIPR-2 expression.PLoS One. 2013 Oct 29;8(10):e77497. doi: 10.1371/journal.pone.0077497. eCollection 2013.
• [3] 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.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] 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.
• [15] Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. J Clin Med. 2020 Feb 3;9(2):405. doi: 10.3390/jcm9020405.