Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHJNNO2)

• DOT Name: T-cell activation Rho GTPase-activating protein (TAGAP)
• Synonyms: T-cell activation GTPase-activating protein
• Gene Name: TAGAP
• Related Disease:
  Autoimmune disease
  Candidemia
  Cowden disease
  Crohn disease
  Multiple sclerosis
  Nervous system inflammation
  Palmoplantar pustulosis
  Psoriasis
  Rheumatoid arthritis
  Ulcerative colitis
  Asthma
  Coeliac disease
  Immune system disorder
  Arthritis
  Inflammation
  Type-1 diabetes
• UniProt ID: TAGAP_HUMAN
• Pfam ID: PF00620
• Sequence:
  MKLRSSHNASKTLNANNMETLIECQSEGDIKEHPLLASCESEDSICQLIEVKKRKKVLSW
  PFLMRRLSPASDFSGALETDLKASLFDQPLSIICGDSDTLPRPIQDILTILCLKGPSTEG
  IFRRAANEKARKELKEELNSGDAVDLERLPVHLLAVVFKDFLRSIPRKLLSSDLFEEWMG
  ALEMQDEEDRIEALKQVADKLPRPNLLLLKHLVYVLHLISKNSEVNRMDSSNLAICIGPN
  MLTLENDQSLSFEAQKDLNNKVKTLVEFLIDNCFEIFGENIPVHSSITSDDSLEHTDSSD
  VSTLQNDSAYDSNDPDVESNSSSGISSPSRQPQVPMATAAGLDSAGPQDAREVSPEPIVS
  TVARLKSSLAQPDRRYSEPSMPSSQECLESRVTNQTLTKSEGDFPVPRVGSRLESEEAED
  PFPEEVFPAVQGKTKRPVDLKIKNLAPGSVLPRALVLKAFSSSSLDASSDSSPVASPSSP
  KRNFFSRHQSFTTKTEKGKPSREIKKHSMSFTFAPHKKVLTKNLSAGSGKSQDFTRDHVP
  RGVRKESQLAGRIVQENGCETHNQTARGFCLRPHALSVDDVFQGADWERPGSPPSYEEAM
  QGPAARLVASESQTVGSMTVGSMRARMLEAHCLLPPLPPAHHVEDSRHRGSKEPLPGHGL
  SPLPERWKQSRTVHASGDSLGHVSGPGRPELLPLRTVSESVQRNKRDCLVRRCSQPVFEA
  DQFQYAKESYI
• Function: May function as a GTPase-activating protein and may play important roles during T-cell activation.
• Reactome Pathway:
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Candidemia	DISVKFN7	Strong	Genetic Variation	[2]
Cowden disease	DISMYKCE	Strong	Altered Expression	[3]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[3]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[4]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[5]
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[6]
Psoriasis	DIS59VMN	Strong	Biomarker	[5]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[7]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[8]
Asthma	DISW9QNS	moderate	Genetic Variation	[9]
Coeliac disease	DISIY60C	moderate	Biomarker	[8]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[10]
Arthritis	DIST1YEL	Limited	Altered Expression	[7]
Inflammation	DISJUQ5T	Limited	Biomarker	[7]
Type-1 diabetes	DIS7HLUB	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[14]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[17]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[18]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[18]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of T-cell activation Rho GTPase-activating protein (TAGAP).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of T-cell activation Rho GTPase-activating protein (TAGAP).	[20]

References

• [1] Identification and in silico analysis of functional SNPs of human TAGAP protein: A comprehensive study.PLoS One. 2018 Jan 12;13(1):e0188143. doi: 10.1371/journal.pone.0188143. eCollection 2018.
• [2] Immunochip SNP array identifies novel genetic variants conferring susceptibility to candidaemia.Nat Commun. 2014 Sep 8;5:4675. doi: 10.1038/ncomms5675.
• [3] T-cell activation Rho GTPase-activating protein expression varies with inflammation location and severity in Crohn's disease.J Surg Res. 2014 Aug;190(2):457-64. doi: 10.1016/j.jss.2014.01.019. Epub 2014 Jan 17.
• [4] Association of rs1738074 polymorphism of TAGAP gene with susceptibility to multiple sclerosis in the Iranian population.Neurosci Lett. 2017 May 1;648:66-69. doi: 10.1016/j.neulet.2017.03.041. Epub 2017 Mar 27.
• [5] T-cell activation RhoGTPase-activating protein plays an important role in T(H)17-cell differentiation.Immunol Cell Biol. 2017 Sep;95(8):729-735. doi: 10.1038/icb.2017.27. Epub 2017 May 2.
• [6] Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity.Nat Genet. 2012 Dec;44(12):1341-8. doi: 10.1038/ng.2467. Epub 2012 Nov 11.
• [7] T cell activation Rho GTPase activating protein (TAGAP) is upregulated in clinical and experimental arthritis.Cytokine. 2018 Apr;104:130-135. doi: 10.1016/j.cyto.2017.10.002. Epub 2017 Oct 7.
• [8] Expression patterns common and unique to ulcerative colitis and celiac disease.Ann Hum Genet. 2019 Mar;83(2):86-94. doi: 10.1111/ahg.12293. Epub 2018 Nov 6.
• [9] Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia.Eur J Hum Genet. 2011 Apr;19(4):458-64. doi: 10.1038/ejhg.2010.191. Epub 2010 Dec 8.
• [10] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.PLoS Genet. 2011 Feb;7(2):e1002004. doi: 10.1371/journal.pgen.1002004. Epub 2011 Feb 24.
• [11] Shared and distinct genetic variants in type 1 diabetes and celiac disease.N Engl J Med. 2008 Dec 25;359(26):2767-77. doi: 10.1056/NEJMoa0807917. Epub 2008 Dec 10.
• [12] 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.
• [13] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [14] 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.
• [15] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [16] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [17] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [18] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [19] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [20] 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.