Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5QD8FG)

• DOT Name: Golgin-45 (BLZF1)
• Synonyms: Basic leucine zipper nuclear factor 1; JEM-1; p45 basic leucine-zipper nuclear factor
• Gene Name: BLZF1
• Related Disease:
  Huntington disease
  Leukemia
  Lyme disease
  Promyelocytic leukaemia
  Smallpox
  Venous thromboembolism
  Brucellosis
  Amyotrophic lateral sclerosis
• UniProt ID: GO45_HUMAN
• Pfam ID: PF08227
• Sequence:
  MTTKNLETKVTVTSSPIRGAGDGMETEEPPKSVEVTSGVQSRKHHSLQSPWKKAVPSESP
  GVLQLGKMLTEKAMEVKAVRILVPKAAITHDIPNKNTKVKSLGHHKGEFLGQSEGVIEPN
  KELSEVKNVLEKLKNSERRLLQDKEGLSNQLRVQTEVNRELKKLLVASVGDDLQYHFERL
  AREKNQLILENEALGRNTAQLSEQLERMSIQCDVWRSKFLASRVMADELTNSRAALQRQN
  RDAHGAIQDLLSEREQFRQEMIATQKLLEELLVSLQWGREQTYSPSVQPHSTAELALTNH
  KLAKAVNSHLLGNVGINNQKKIPSTVEFCSTPAEKMAETVLRILDPVTCKESSPDNPFFE
  SSPTTLLATKKNIGRFHPYTRYENITFNCCNHCRGELIAL
• Function: Required for normal Golgi structure and for protein transport from the endoplasmic reticulum (ER) through the Golgi apparatus to the cell surface.
• Tissue Specificity: Detected in adrenal gland .
• Reactome Pathway: Golgi Cisternae Pericentriolar Stack Reorganization (R-HSA-162658)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Huntington disease	DISQPLA4	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Lyme disease	DISO70G5	Strong	Biomarker	[3]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[4]
Smallpox	DIS9EABZ	Strong	Genetic Variation	[5]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[6]
Brucellosis	DISEAYGH	Disputed	Biomarker	[7]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Golgin-45 (BLZF1).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Golgin-45 (BLZF1).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Golgin-45 (BLZF1).	[20]

11 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 Golgin-45 (BLZF1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Golgin-45 (BLZF1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Golgin-45 (BLZF1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Golgin-45 (BLZF1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Golgin-45 (BLZF1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Golgin-45 (BLZF1).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Golgin-45 (BLZF1).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Golgin-45 (BLZF1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Golgin-45 (BLZF1).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Golgin-45 (BLZF1).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Golgin-45 (BLZF1).	[22]

References

• [1] CAG trinucleotide RNA repeats interact with RNA-binding proteins.Am J Hum Genet. 1996 Sep;59(3):561-9.
• [2] JEM-1, a novel gene encoding a leucine-zipper nuclear factor upregulated during retinoid-induced maturation of NB4 promyelocytic leukaemia.Oncogene. 1997 Apr 3;14(13):1563-70. doi: 10.1038/sj.onc.1200995.
• [3] Evaluation of genetic divergence of borrelial isolates from Lyme disease patients in Hokkaido, Japan, by rRNA gene probes.J Clin Microbiol. 1993 Aug;31(8):2044-8. doi: 10.1128/jcm.31.8.2044-2048.1993.
• [4] Expression patterns of the JEM-1 gene in normal and tumor cells: ubiquity contrasting with a faint, but retinoid-induced, mRNA expression in promyelocytic NB4 cells.Leukemia. 1998 Nov;12(11):1733-40. doi: 10.1038/sj.leu.2401173.
• [5] Inhibition of type III interferon activity by orthopoxvirus immunomodulatory proteins.J Interferon Cytokine Res. 2010 Mar;30(3):123-34. doi: 10.1089/jir.2009.0049.
• [6] A genome-wide association study of venous thromboembolism identifies risk variants in chromosomes 1q24.2 and 9q.J Thromb Haemost. 2012 Aug;10(8):1521-31. doi: 10.1111/j.1538-7836.2012.04810.x.
• [7] Diminished production of T helper 1 cytokines correlates with T cell unresponsiveness to Brucella cytoplasmic proteins in chronic human brucellosis.J Infect Dis. 2002 Jul 15;186(2):252-9. doi: 10.1086/341449. Epub 2002 Jun 17.
• [8] Developmentally Regulated RNA-binding Protein 1 (Drb1)/RNA-binding Motif Protein 45 (RBM45), a Nuclear-Cytoplasmic Trafficking Protein, Forms TAR DNA-binding Protein 43 (TDP-43)-mediated Cytoplasmic Aggregates.J Biol Chem. 2016 Jul 15;291(29):14996-5007. doi: 10.1074/jbc.M115.712232. Epub 2016 May 12.
• [9] 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.
• [10] 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.
• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro: estrogen receptor dependent or independent pathways of raloxifene. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):281-9.
• [14] 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.
• [15] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [16] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [17] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.