Details of Drug Off-Target (DOT)

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

DOT Name PDZ domain-containing protein GIPC1 (GIPC1)
Synonyms GAIP C-terminus-interacting protein; RGS-GAIP-interacting protein; RGS19-interacting protein 1; Synectin; Tax interaction protein 2; TIP-2
Gene Name GIPC1
Related Disease
Advanced cancer ( )
Anemia ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Deafness ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Glioma ( )
Immunodeficiency ( )
Kidney cancer ( )
Kidney neoplasm ( )
leukaemia ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant glioma ( )
Neoplasm ( )
Oculopharyngodistal myopathy 2 ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Pancreatic adenocarcinoma ( )
Pancreatic cancer ( )
Pancreatic tumour ( )
Pheochromocytoma ( )
Renal carcinoma ( )
Stomach cancer ( )
Cervical cancer ( )
Cervical carcinoma ( )
Type-1/2 diabetes ( )
Oculopharyngodistal myopathy ( )
Matthew-Wood syndrome ( )
Pancreatic ductal carcinoma ( )
Pneumonia ( )
UniProt ID
GIPC1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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Pfam ID
PF00595
Sequence
MPLGLGRRKKAPPLVENEEAEPGRGGLGVGEPGPLGGGGSGGPQMGLPPPPPALRPRLVF
HTQLAHGSPTGRIEGFTNVKELYGKIAEAFRLPTAEVMFCTLNTHKVDMDKLLGGQIGLE
DFIFAHVKGQRKEVEVFKSEDALGLTITDNGAGYAFIKRIKEGSVIDHIHLISVGDMIEA
INGQSLLGCRHYEVARLLKELPRGRTFTLKLTEPRKAFDMISQRSAGGRPGSGPQLGTGR
GTLRLRSRGPATVEDLPSAFEEKAIEKVDDLLESYMGIRDTELAATMVELGKDKRNPDEL
AEALDERLGDFAFPDEFVFDVWGAIGDAKVGRY
Function May be involved in G protein-linked signaling.
Tissue Specificity Widely expressed . Expressed in skeletal muscle (at protein level) .
Reactome Pathway
FGFR1c ligand binding and activation (R-HSA-190373 )
FGFR1b ligand binding and activation (R-HSA-190370 )

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Anemia DISTVL0C Strong Genetic Variation [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Breast neoplasm DISNGJLM Strong Biomarker [3]
Colorectal carcinoma DIS5PYL0 Strong Posttranslational Modification [4]
Colorectal neoplasm DISR1UCN Strong Altered Expression [5]
Deafness DISKCLH4 Strong Biomarker [6]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [4]
Gastric cancer DISXGOUK Strong Altered Expression [7]
Glioma DIS5RPEH Strong Biomarker [8]
Immunodeficiency DIS093I0 Strong Biomarker [4]
Kidney cancer DISBIPKM Strong Biomarker [3]
Kidney neoplasm DISBNZTN Strong Altered Expression [7]
leukaemia DISS7D1V Strong Altered Expression [7]
Leukemia DISNAKFL Strong Altered Expression [7]
Lung cancer DISCM4YA Strong Altered Expression [7]
Lung carcinoma DISTR26C Strong Altered Expression [7]
Malignant glioma DISFXKOV Strong Biomarker [9]
Neoplasm DISZKGEW Strong Biomarker [10]
Oculopharyngodistal myopathy 2 DIS3LUS4 Strong Autosomal dominant [11]
Ovarian cancer DISZJHAP Strong Biomarker [4]
Ovarian neoplasm DISEAFTY Strong Biomarker [4]
Pancreatic adenocarcinoma DISKHX7S Strong Biomarker [12]
Pancreatic cancer DISJC981 Strong Biomarker [4]
Pancreatic tumour DIS3U0LK Strong Biomarker [13]
Pheochromocytoma DIS56IFV Strong Altered Expression [14]
Renal carcinoma DISER9XT Strong Biomarker [3]
Stomach cancer DISKIJSX Strong Altered Expression [7]
Cervical cancer DISFSHPF moderate Altered Expression [15]
Cervical carcinoma DIST4S00 moderate Altered Expression [15]
Type-1/2 diabetes DISIUHAP moderate Biomarker [16]
Oculopharyngodistal myopathy DISGCD9O Supportive Autosomal dominant [17]
Matthew-Wood syndrome DISA7HR7 Disputed Biomarker [18]
Pancreatic ductal carcinoma DIS26F9Q Disputed Biomarker [18]
Pneumonia DIS8EF3M Limited Biomarker [19]
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⏷ Show the Full List of 36 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved PDZ domain-containing protein GIPC1 (GIPC1) decreases the response to substance of Arsenic trioxide. [31]
Gemcitabine DMSE3I7 Approved PDZ domain-containing protein GIPC1 (GIPC1) affects the response to substance of Gemcitabine. [32]
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4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of PDZ domain-containing protein GIPC1 (GIPC1). [20]
Estradiol DMUNTE3 Approved Estradiol decreases the phosphorylation of PDZ domain-containing protein GIPC1 (GIPC1). [22]
G1 DMTV42K Phase 1/2 G1 decreases the phosphorylation of PDZ domain-containing protein GIPC1 (GIPC1). [22]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of PDZ domain-containing protein GIPC1 (GIPC1). [28]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [21]
Quercetin DM3NC4M Approved Quercetin increases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [23]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [24]
Marinol DM70IK5 Approved Marinol decreases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [25]
Selenium DM25CGV Approved Selenium increases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [26]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [27]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [26]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [29]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of PDZ domain-containing protein GIPC1 (GIPC1). [30]
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⏷ Show the Full List of 9 Drug(s)

References

1 NRP-1 interacts with GIPC1 and SYX to activate p38 MAPK signaling and cancer stem cell survival.Mol Carcinog. 2019 Apr;58(4):488-499. doi: 10.1002/mc.22943. Epub 2018 Dec 21.
2 Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2-) advanced breast cancer patients: New insights beyond clinical trials. The EVA study.Breast. 2017 Oct;35:115-121. doi: 10.1016/j.breast.2017.06.043. Epub 2017 Jul 13.
3 RGS-GAIP-interacting protein controls breast cancer progression.Mol Cancer Res. 2010 Dec;8(12):1591-600. doi: 10.1158/1541-7786.MCR-10-0209. Epub 2010 Oct 27.
4 Therapeutic implications of GIPC1 silencing in cancer.PLoS One. 2010 Dec 30;5(12):e15581. doi: 10.1371/journal.pone.0015581.
5 Molecular cloning and characterization of human GIPC2, a novel gene homologous to human GIPC1 and Xenopus Kermit.Int J Oncol. 2002 Mar;20(3):571-6.
6 Genotype-phenotype relationship in three cases with overlapping 19p13.12 microdeletions.Eur J Hum Genet. 2010 Dec;18(12):1302-9. doi: 10.1038/ejhg.2010.115. Epub 2010 Jul 21.
7 Expression of human GIPC1 in normal tissues, cancer cell lines, and primary tumors.Int J Mol Med. 2002 May;9(5):509-13.
8 Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression.Tumour Biol. 2016 Oct;37(10):13777-13788. doi: 10.1007/s13277-016-5138-3. Epub 2016 Aug 1.
9 miRNA-124-3p/neuropilin-1(NRP-1) axis plays an important role in mediating glioblastoma growth and angiogenesis.Int J Cancer. 2018 Aug 1;143(3):635-644. doi: 10.1002/ijc.31329. Epub 2018 Mar 2.
10 Knockdown of ovarian cancer amplification target ADRM1 leads to downregulation of GIPC1 and upregulation of RECK.Genes Chromosomes Cancer. 2011 Jun;50(6):434-41. doi: 10.1002/gcc.20868. Epub 2011 Mar 22.
11 Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy. Am J Hum Genet. 2020 Jun 4;106(6):793-804. doi: 10.1016/j.ajhg.2020.04.011. Epub 2020 May 14.
12 Targeting GIPC/synectin in pancreatic cancer inhibits tumor growth.Clin Cancer Res. 2009 Jun 15;15(12):4095-103. doi: 10.1158/1078-0432.CCR-08-2837. Epub 2009 Jun 9.
13 [GIPC: a new target for therapy in pancreatic adenocarcinoma?].Verh Dtsch Ges Pathol. 2007;91:286-93.
14 Protein interactions with the glucose transporter binding protein GLUT1CBP that provide a link between GLUT1 and the cytoskeleton.Mol Biol Cell. 1999 Apr;10(4):819-32. doi: 10.1091/mbc.10.4.819.
15 Functional proteomics, human genetics and cancer biology of GIPC family members.Exp Mol Med. 2013 Jun 7;45(6):e26. doi: 10.1038/emm.2013.49.
16 Inferring pleiotropy by network analysis: linked diseases in the human PPI network.BMC Syst Biol. 2011 Oct 31;5:179. doi: 10.1186/1752-0509-5-179.
17 5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy. Brain. 2021 Mar 3;144(2):601-614. doi: 10.1093/brain/awaa426.
18 Silencing of Neuropilins and GIPC1 in pancreatic ductal adenocarcinoma exerts multiple cellular and molecular antitumor effects.Sci Rep. 2019 Oct 29;9(1):15471. doi: 10.1038/s41598-019-51881-8.
19 Indirect (herd) protection, following pneumococcal conjugated vaccines introduction: A systematic review of the literature.Vaccine. 2017 May 19;35(22):2882-2891. doi: 10.1016/j.vaccine.2017.04.032. Epub 2017 Apr 24.
20 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
21 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
22 The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
23 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.
24 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
25 JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
26 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
27 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
28 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.
29 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
30 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
31 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.
32 GAIP interacting protein C-terminus regulates autophagy and exosome biogenesis of pancreatic cancer through metabolic pathways. PLoS One. 2014 Dec 3;9(12):e114409. doi: 10.1371/journal.pone.0114409. eCollection 2014.