Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7X0W3N)

• DOT Name: Golgi apparatus protein 1 (GLG1)
• Synonyms: CFR-1; Cysteine-rich fibroblast growth factor receptor; E-selectin ligand 1; ESL-1; Golgi sialoglycoprotein MG-160
• Gene Name: GLG1
• Related Disease:
  Advanced cancer
  Astrocytoma
  Brain neoplasm
  Ewing sarcoma
  Stomach cancer
  Varicose veins
• UniProt ID: GSLG1_HUMAN
• Pfam ID: PF00839
• Sequence:
  MAACGRVRRMFRLSAALHLLLLFAAGAEKLPGQGVHSQGQGPGANFVSFVGQAGGGGPAG
  QQLPQLPQSSQLQQQQQQQQQQQQPQPPQPPFPAGGPPARRGGAGAGGGWKLAEEESCRE
  DVTRVCPKHTWSNNLAVLECLQDVREPENEISSDCNHLLWNYKLNLTTDPKFESVAREVC
  KSTITEIKECADEPVGKGYMVSCLVDHRGNITEYQCHQYITKMTAIIFSDYRLICGFMDD
  CKNDINILKCGSIRLGEKDAHSQGEVVSCLEKGLVKEAEEREPKIQVSELCKKAILRVAE
  LSSDDFHLDRHLYFACRDDRERFCENTQAGEGRVYKCLFNHKFEESMSEKCREALTTRQK
  LIAQDYKVSYSLAKSCKSDLKKYRCNVENLPRSREARLSYLLMCLESAVHRGRQVSSECQ
  GEMLDYRRMLMEDFSLSPEIILSCRGEIEHHCSGLHRKGRTLHCLMKVVRGEKGNLGMNC
  QQALQTLIQETDPGADYRIDRALNEACESVIQTACKHIRSGDPMILSCLMEHLYTEKMVE
  DCEHRLLELQYFISRDWKLDPVLYRKCQGDASRLCHTHGWNETSEFMPQGAVFSCLYRHA
  YRTEEQGRRLSRECRAEVQRILHQRAMDVKLDPALQDKCLIDLGKWCSEKTETGQELECL
  QDHLDDLVVECRDIVGNLTELESEDIQIEALLMRACEPIIQNFCHDVADNQIDSGDLMEC
  LIQNKHQKDMNEKCAIGVTHFQLVQMKDFRFSYKFKMACKEDVLKLCPNIKKKVDVVICL
  STTVRNDTLQEAKEHRVSLKCRRQLRVEELEMTEDIRLEPDLYEACKSDIKNFCSAVQYG
  NAQIIECLKENKKQLSTRCHQKVFKLQETEMMDPELDYTLMRVCKQMIKRFCPEADSKTM
  LQCLKQNKNSELMDPKCKQMITKRQITQNTDYRLNPMLRKACKADIPKFCHGILTKAKDD
  SELEGQVISCLKLRYADQRLSSDCEDQIRIIIQESALDYRLDPQLQLHCSDEISSLCAEE
  AAAQEQTGQVEECLKVNLLKIKTELCKKEVLNMLKESKADIFVDPVLHTACALDIKHHCA
  AITPGRGRQMSCLMEALEDKRVRLQPECKKRLNDRIEMWSYAAKVAPADGFSDLAMQVMT
  SPSKNYILSVISGSICILFLIGLMCGRITKRVTRELKDR
• Function: Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils).
• Tissue Specificity: Widely expressed. Highest levels in pancreas, skeletal muscle, placenta, heart, testis and ovary. Also found in the kidney, liver, lung and brain.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Astrocytoma	DISL3V18	Strong	Biomarker	[1]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[1]
Ewing sarcoma	DISQYLV3	Strong	Biomarker	[2]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[3]
Varicose veins	DISIMBN2	moderate	Genetic Variation	[4]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Golgi apparatus protein 1 (GLG1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Golgi apparatus protein 1 (GLG1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Golgi apparatus protein 1 (GLG1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Golgi apparatus protein 1 (GLG1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgi apparatus protein 1 (GLG1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Golgi apparatus protein 1 (GLG1).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Golgi apparatus protein 1 (GLG1).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Golgi apparatus protein 1 (GLG1).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Golgi apparatus protein 1 (GLG1).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Golgi apparatus protein 1 (GLG1).	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Golgi apparatus protein 1 (GLG1).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Golgi apparatus protein 1 (GLG1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Golgi apparatus protein 1 (GLG1).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Golgi apparatus protein 1 (GLG1).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Golgi apparatus protein 1 (GLG1).	[18]

References

• [1] Identification of MG-160, a FGF binding medial Golgi sialoglycoprotein, in brain tumors: an index of malignancy in astrocytomas.Int J Oncol. 2003 May;22(5):1045-9.
• [2] Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets.Oncotarget. 2017 Aug 4;9(2):1587-1601. doi: 10.18632/oncotarget.20098. eCollection 2018 Jan 5.
• [3] Cysteine-rich fibroblast growth factor receptor 1, a new marker for precancerous epithelial lesions defined by the human monoclonal antibody PAM-1.Cancer Res. 2003 May 1;63(9):2052-61.
• [4] Clinical and Genetic Determinants of Varicose Veins.Circulation. 2018 Dec 18;138(25):2869-2880. doi: 10.1161/CIRCULATIONAHA.118.035584.
• [5] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] 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.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] 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.
• [13] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [14] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [15] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.