Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1TN2KT)

• DOT Name: G patch domain and ankyrin repeat-containing protein 1 (GPANK1)
• Synonyms: Ankyrin repeat domain-containing protein 59; G patch domain-containing protein 10; HLA-B-associated transcript 4; Protein G5
• Gene Name: GPANK1
• Related Disease:
  Epstein barr virus infection
  Follicular lymphoma
  Lymphoma, non-Hodgkin, familial
  Membranous glomerulonephritis
  Myasthenia gravis
  Rheumatoid arthritis
  Type-1 diabetes
  Systemic lupus erythematosus
  Non-hodgkin lymphoma
• UniProt ID: GPAN1_HUMAN
• Pfam ID: PF13637 ; PF01585
• Sequence:
  MSRPLLITFTPATDPSDLWKDGQQQPQPEKPESTLDGAAARAFYEALIGDESSAPDSQRS
  QTEPARERKRKKRRIMKAPAAEAVAEGASGRHGQGRSLEAEDKMTHRILRAAQEGDLPEL
  RRLLEPHEAGGAGGNINARDAFWWTPLMCAARAGQGAAVSYLLGRGAAWVGVCELSGRDA
  AQLAEEAGFPEVARMVRESHGETRSPENRSPTPSLQYCENCDTHFQDSNHRTSTAHLLSL
  SQGPQPPNLPLGVPISSPGFKLLLRGGWEPGMGLGPRGEGRANPIPTVLKRDQEGLGYRS
  APQPRVTHFPAWDTRAVAGRERPPRVATLSWREERRREEKDRAWERDLRTYMNLEF

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epstein barr virus infection	DISOO0WT	Strong	Genetic Variation	[1]
Follicular lymphoma	DISVEUR6	Strong	Genetic Variation	[2]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[3]
Membranous glomerulonephritis	DISFSUKQ	Strong	Genetic Variation	[4]
Myasthenia gravis	DISELRCI	Strong	Genetic Variation	[5]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[6]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[7]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[8]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Genetic Variation	[3]

8 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 G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[14]
Menadione	DMSJDTY	Approved	Menadione affects the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[14]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[16]

3 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 G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[17]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of G patch domain and ankyrin repeat-containing protein 1 (GPANK1).	[18]

References

• [1] A genome-wide integrative genomic study localizes genetic factors influencing antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1).PLoS Genet. 2013;9(1):e1003147. doi: 10.1371/journal.pgen.1003147. Epub 2013 Jan 10.
• [2] Variations in chromosomes 9 and 6p21.3 with risk of non-Hodgkin lymphoma.Cancer Epidemiol Biomarkers Prev. 2011 Jan;20(1):42-9. doi: 10.1158/1055-9965.EPI-10-0638. Epub 2010 Dec 10.
• [3] Interactions within the MHC contribute to the genetic architecture of celiac disease.PLoS One. 2017 Mar 10;12(3):e0172826. doi: 10.1371/journal.pone.0172826. eCollection 2017.
• [4] Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.N Engl J Med. 2011 Feb 17;364(7):616-26. doi: 10.1056/NEJMoa1009742.
• [5] Risk for myasthenia gravis maps to a (151) ProAla change in TNIP1 and to human leukocyte antigen-B*08.Ann Neurol. 2012 Dec;72(6):927-35. doi: 10.1002/ana.23691. Epub 2012 Oct 10.
• [6] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [7] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [8] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [9] 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.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 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.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] 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.
• [15] 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.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.