Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFET2YM)

DOT Name Growth factor receptor-bound protein 14 (GRB14)
Synonyms GRB14 adapter protein
Gene Name GRB14
Related Disease
Advanced cancer ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Colorectal carcinoma ( )
Obesity ( )
Metastatic malignant neoplasm ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
Non-insulin dependent diabetes ( )
UniProt ID
GRB14_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2AUG; 2AUH; 4K81
Pfam ID
PF08947 ; PF00169 ; PF00788 ; PF00017
Sequence
MTTSLQDGQSAASRAAARDSPLAAQVCGAAQGRGDAHDLAPAPWLHARALLPLPDGTRGC
AADRRKKKDLDVPEMPSIPNPFPELCCSPFTSVLSADLFPKANSRKKQVIKVYSEDETSR
ALDVPSDITARDVCQLLILKNHYIDDHSWTLFEHLPHIGVERTIEDHELVIEVLSNWGIE
EENKLYFRKNYAKYEFFKNPMYFFPEHMVSFATETNGEISPTQILQMFLSSSTYPEIHGF
LHAKEQGKKSWKKIYFFLRRSGLYFSTKGTSKEPRHLQFFSEFGNSDIYVSLAGKKKHGA
PTNYGFCFKPNKAGGPRDLKMLCAEEEQSRTCWVTAIRLLKYGMQLYQNYMHPYQGRSGC
SSQSISPMRSISENSLVAMDFSGQKSRVIENPTEALSVAVEEGLAWRKKGCLRLGTHGSP
TASSQSSATNMAIHRSQPWFHHKISRDEAQRLIIQQGLVDGVFLVRDSQSNPKTFVLSMS
HGQKIKHFQIIPVEDDGEMFHTLDDGHTRFTDLIQLVEFYQLNKGVLPCKLKHYCARIAL
Function
Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.
Tissue Specificity Expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart and skeletal muscle.
Reactome Pathway
Tie2 Signaling (R-HSA-210993 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Bladder cancer DISUHNM0 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [1]
Obesity DIS47Y1K Strong Genetic Variation [4]
Metastatic malignant neoplasm DIS86UK6 moderate Altered Expression [5]
Thyroid cancer DIS3VLDH moderate Altered Expression [5]
Thyroid gland carcinoma DISMNGZ0 moderate Altered Expression [5]
Thyroid tumor DISLVKMD moderate Altered Expression [5]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [6]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [8]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [9]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [10]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [11]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [14]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Growth factor receptor-bound protein 14 (GRB14). [15]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [16]
Phenobarbital DMXZOCG Approved Phenobarbital increases the expression of Growth factor receptor-bound protein 14 (GRB14). [17]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [18]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Growth factor receptor-bound protein 14 (GRB14). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Growth factor receptor-bound protein 14 (GRB14). [21]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Growth factor receptor-bound protein 14 (GRB14). [7]
Deguelin DMXT7WG Investigative Deguelin increases the expression of Growth factor receptor-bound protein 14 (GRB14). [22]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Growth factor receptor-bound protein 14 (GRB14). [23]
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⏷ Show the Full List of 16 Drug(s)
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 Growth factor receptor-bound protein 14 (GRB14). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Growth factor receptor-bound protein 14 (GRB14). [20]
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References

1 High expression of growth factor receptor-bound protein 14 predicts poor prognosis for colorectal cancer patients.Biotechnol Lett. 2016 Jun;38(6):1043-7. doi: 10.1007/s10529-016-2077-4. Epub 2016 Mar 10.
2 Identification of new hub genes associated with bladder carcinoma via bioinformatics analysis.Tumori. 2015 Jan-Feb;101(1):117-22. doi: 10.5301/tj.5000196. Epub 2015 Feb 6.
3 FGF receptor phosphotyrosine 766 is a target for Grb14 to inhibit MDA-MB-231 human breast cancer cell signaling.Anticancer Res. 2005 Nov-Dec;25(6B):3877-82.
4 Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects.Eur J Hum Genet. 2016 Jun;24(6):903-10. doi: 10.1038/ejhg.2015.212. Epub 2015 Sep 23.
5 The insulin resistance Grb14 adaptor protein promotes thyroid cancer ret signaling and progression.Oncogene. 2012 Sep 6;31(36):4012-21. doi: 10.1038/onc.2011.569. Epub 2011 Dec 12.
6 Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
7 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
8 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.
9 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
10 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
11 Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
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 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
14 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
16 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
17 Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
18 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
19 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
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.
21 Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
22 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
23 Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.