Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMYNY7A)

• DOT Name: Golgi resident protein GCP60 (ACBD3)
• Synonyms: Acyl-CoA-binding domain-containing protein 3; Golgi complex-associated protein 1; GOCAP1; Golgi phosphoprotein 1; GOLPH1; PBR- and PKA-associated protein 7; Peripheral benzodiazepine receptor-associated protein PAP7
• Gene Name: ACBD3
• Related Disease:
  Breast cancer
  Breast carcinoma
  Enterovirus infection
  Fatty liver disease
  Huntington disease
• UniProt ID: GCP60_HUMAN
• PDB ID: 2N72; 2N73; 5LZ1; 5LZ3; 5LZ6; 5TDQ; 6HLN; 6HLT; 6HLV; 6HLW; 6HM8; 6HMV
• Pfam ID: PF00887 ; PF13897
• Sequence:
  MAAVLNAERLEVSVDGLTLSPDPEERPGAEGAPLLPPPLPPPSPPGSGRGPGASGEQPEP
  GEAAAGGAAEEARRLEQRWGFGLEELYGLALRFFKEKDGKAFHPTYEEKLKLVALHKQVL
  MGPYNPDTCPEVGFFDVLGNDRRREWAALGNMSKEDAMVEFVKLLNRCCHLFSTYVASHK
  IEKEEQEKKRKEEEERRRREEEERERLQKEEEKRRREEEERLRREEEERRRIEEERLRLE
  QQKQQIMAALNSQTAVQFQQYAAQQYPGNYEQQQILIRQLQEQHYQQYMQQLYQVQLAQQ
  QAALQKQQEVVVAGSSLPTSSKVNATVPSNMMSVNGQAKTHTDSSEKELEPEAAEEALEN
  GPKESLPVIAAPSMWTRPQIKDFKEKIQQDADSVITVGRGEVVTVRVPTHEEGSYLFWEF
  ATDNYDIGFGVYFEWTDSPNTAVSVHVSESSDDDEEEEENIGCEEKAKKNANKPLLDEIV
  PVYRRDCHEEVYAGSHQYPGRGVYLLKFDNSYSLWRSKSVYYRVYYTR
• Function: Involved in the maintenance of Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and Golgi. Involved in hormone-induced steroid biosynthesis in testicular Leydig cells. Recruits PI4KB to the Golgi apparatus membrane; enhances the enzyme activity of PI4KB activity via its membrane recruitment thereby increasing the local concentration of the substrate in the vicinity of the kinase ; (Microbial infection) Plays an essential role in Aichi virus RNA replication by recruiting PI4KB at the viral replication sites.
• Tissue Specificity: Ubiquitous, with highest expression in testis and ovary.
• KEGG Pathway: Salmonella infection (hsa05132)
• Reactome Pathway: Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Enterovirus infection	DISH2UDP	Strong	Biomarker	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Huntington disease	DISQPLA4	Strong	Biomarker	[4]

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 Golgi resident protein GCP60 (ACBD3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Golgi resident protein GCP60 (ACBD3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Golgi resident protein GCP60 (ACBD3).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Golgi resident protein GCP60 (ACBD3).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Golgi resident protein GCP60 (ACBD3).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Golgi resident protein GCP60 (ACBD3).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Golgi resident protein GCP60 (ACBD3).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Golgi resident protein GCP60 (ACBD3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Golgi resident protein GCP60 (ACBD3).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Golgi resident protein GCP60 (ACBD3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Golgi resident protein GCP60 (ACBD3).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Golgi resident protein GCP60 (ACBD3).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Golgi resident protein GCP60 (ACBD3).	[17]

References

• [1] Overexpressed ACBD3 has prognostic value in human breast cancer and promotes the self-renewal potential of breast cancer cells by activating the Wnt/beta-catenin signaling pathway.Exp Cell Res. 2018 Feb 1;363(1):39-47. doi: 10.1016/j.yexcr.2018.01.003. Epub 2018 Jan 4.
• [2] Structural basis for hijacking of the host ACBD3 protein by bovine and porcine enteroviruses and kobuviruses.Arch Virol. 2020 Feb;165(2):355-366. doi: 10.1007/s00705-019-04490-9. Epub 2019 Dec 16.
• [3] circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role against Hepatic Steatosis.Oxid Med Cell Longev. 2017;2017:3960197. doi: 10.1155/2017/3960197. Epub 2017 Sep 5.
• [4] Acyl-CoA-Binding Domain-Containing 3 (ACBD3; PAP7; GCP60): A Multi-Functional Membrane Domain Organizer.Int J Mol Sci. 2019 Apr 24;20(8):2028. doi: 10.3390/ijms20082028.
• [5] 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.
• [6] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] 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.
• [11] 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.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] 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.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] 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.