Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKX1KEC)

• DOT Name: GRB2-associated-binding protein 3 (GAB3)
• Synonyms: GRB2-associated binder 3; Growth factor receptor bound protein 2-associated protein 3
• Gene Name: GAB3
• Related Disease:
  Advanced cancer
  Colitis
  Colorectal carcinoma
  Glioma
  Hemochromatosis
  Neoplasm
  Type-1 diabetes
• UniProt ID: GAB3_HUMAN
• Pfam ID: PF00169
• Sequence:
  MSAGDAVCTGWLVKSPPERKLQRYAWRKRWFVLRRGRMSGNPDVLEYYRNKHSSKPIRVI
  DLSECAVWKHVGPSFVRKEFQNNFVFIVKTTSRTFYLVAKTEQEMQVWVHSISQVCNLGH
  LEDGADSMESLSYTPSSLQPSSASSLLTAHAASSSLPRDDPNTNAVATEETRSESELLFL
  PDYLVLSNCETGRLHHTSLPTRCDSWSNSDRSLEQASFDDVFVDCLQPLPSSHLVHPSCH
  GSGAQEVPSSRPQAALIWSREINGPPRDHLSSSPLLESSLSSTIQVDKNQGSLPCGAKEL
  DIMSNTPPPRPPKPSHLSERRQEEWSTHSGSKKPECTLVPRRISLSGLDNMRTWKADVEG
  QSLRHRDKRLSLNLPCRFSPMYPTASASIEDSYVPMSPQAGASGLGPHCSPDDYIPMNSG
  SISSPLPELPANLEPPPVNRDLKPQRKSRPPPLDLRNLSIIREHASLTRTRTVPCSRTSF
  LSPERNGINSARFFANPVSREDEESYIEMEEHRTASSLSSGALTWTKKFSLDYLALDFNS
  ASPAPMQQKLLLSEEQRVDYVQVDEQKTQALQSTKQEWTDERQSKV
• Reactome Pathway: Signaling by CSF1 (M-CSF) in myeloid cells (R-HSA-9680350)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[1]
Hemochromatosis	DISAPY0H	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[5]

6 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 GRB2-associated-binding protein 3 (GAB3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of GRB2-associated-binding protein 3 (GAB3).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GRB2-associated-binding protein 3 (GAB3).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of GRB2-associated-binding protein 3 (GAB3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of GRB2-associated-binding protein 3 (GAB3).	[11]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of GRB2-associated-binding protein 3 (GAB3).	[12]

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 decreases the methylation of GRB2-associated-binding protein 3 (GAB3).	[10]

References

• [1] Gab3 overexpression in human glioma mediates Akt activation and tumor cell proliferation.PLoS One. 2017 Mar 14;12(3):e0173473. doi: 10.1371/journal.pone.0173473. eCollection 2017.
• [2] Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8(+) T-Cell Activation.Front Immunol. 2019 Mar 18;10:486. doi: 10.3389/fimmu.2019.00486. eCollection 2019.
• [3] Gab3 is required for human colorectal cancer cell proliferation.Biochem Biophys Res Commun. 2017 Mar 18;484(4):719-725. doi: 10.1016/j.bbrc.2017.01.095. Epub 2017 Jan 20.
• [4] Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation?.Hum Mol Genet. 2017 May 15;26(10):1966-1978. doi: 10.1093/hmg/ddx082.
• [5] Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.Nat Genet. 2009 Jun;41(6):703-7. doi: 10.1038/ng.381. Epub 2009 May 10.
• [6] 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.
• [7] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [11] 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.
• [12] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.