Details of Drug Off-Target (DOT)

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

DOT Name PDZ and LIM domain protein 2 (PDLIM2)
Synonyms PDZ-LIM protein mystique
Gene Name PDLIM2
Related Disease
Castration-resistant prostate carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Adult T-cell leukemia/lymphoma ( )
Advanced cancer ( )
Anaplastic large cell lymphoma ( )
Autoimmune disease ( )
Bladder cancer ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Esophageal squamous cell carcinoma ( )
Human T-lymphotropic virus 1 infectious disease ( )
Lung cancer ( )
Lung carcinoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Meningioma ( )
Schwannoma ( )
Breast cancer ( )
Breast carcinoma ( )
Focal segmental glomerulosclerosis ( )
Membranous glomerulonephritis ( )
Neoplasm ( )
Triple negative breast cancer ( )
UniProt ID
PDLI2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2PA1; 3PDV
Pfam ID
PF15936 ; PF00412 ; PF00595
Sequence
MALTVDVAGPAPWGFRITGGRDFHTPIMVTKVAERGKAKDADLRPGDIIVAINGESAEGM
LHAEAQSKIRQSPSPLRLQLDRSQATSPGQTNGDSSLEVLATRFQGSVRTYTESQSSLRS
SYSSPTSLSPRAGSPFSPPPSSSSLTGEAAISRSFQSLACSPGLPAADRLSYSGRPGSRQ
AGLGRAGDSAVLVLPPSPGPRSSRPSMDSEGGSLLLDEDSEVFKMLQENREGRAAPRQSS
SFRLLQEALEAEERGGTPAFLPSSLSPQSSLPASRALATPPKLHTCEKCSTSIANQAVRI
QEGRYRHPGCYTCADCGLNLKMRGHFWVGDELYCEKHARQRYSAPATLSSRA
Function
Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity.
KEGG Pathway
Cytoskeleton in muscle cells (hsa04820 )

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Castration-resistant prostate carcinoma DISVGAE6 Definitive Biomarker [1]
Prostate cancer DISF190Y Definitive Biomarker [1]
Prostate carcinoma DISMJPLE Definitive Biomarker [1]
Adult T-cell leukemia/lymphoma DIS882XU Strong Biomarker [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Anaplastic large cell lymphoma DISP4D1R Strong Altered Expression [4]
Autoimmune disease DISORMTM Strong Biomarker [5]
Bladder cancer DISUHNM0 Strong Posttranslational Modification [6]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [7]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [8]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [9]
Human T-lymphotropic virus 1 infectious disease DISN5C4M Strong Genetic Variation [2]
Lung cancer DISCM4YA Strong Altered Expression [10]
Lung carcinoma DISTR26C Strong Biomarker [10]
Ovarian cancer DISZJHAP Strong Biomarker [8]
Ovarian neoplasm DISEAFTY Strong Biomarker [8]
Urinary bladder cancer DISDV4T7 Strong Posttranslational Modification [6]
Urinary bladder neoplasm DIS7HACE Strong Posttranslational Modification [6]
Meningioma DISPT4TG moderate Biomarker [11]
Schwannoma DISTTVLA moderate Biomarker [11]
Breast cancer DIS7DPX1 Limited Altered Expression [12]
Breast carcinoma DIS2UE88 Limited Altered Expression [12]
Focal segmental glomerulosclerosis DISJNHH0 Limited Altered Expression [13]
Membranous glomerulonephritis DISFSUKQ Limited Altered Expression [13]
Neoplasm DISZKGEW Limited Biomarker [12]
Triple negative breast cancer DISAMG6N Limited Biomarker [12]
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⏷ Show the Full List of 26 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of PDZ and LIM domain protein 2 (PDLIM2). [14]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of PDZ and LIM domain protein 2 (PDLIM2). [15]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of PDZ and LIM domain protein 2 (PDLIM2). [16]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of PDZ and LIM domain protein 2 (PDLIM2). [17]
Testosterone DM7HUNW Approved Testosterone increases the expression of PDZ and LIM domain protein 2 (PDLIM2). [17]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of PDZ and LIM domain protein 2 (PDLIM2). [18]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of PDZ and LIM domain protein 2 (PDLIM2). [19]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of PDZ and LIM domain protein 2 (PDLIM2). [20]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of PDZ and LIM domain protein 2 (PDLIM2). [22]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 decreases the expression of PDZ and LIM domain protein 2 (PDLIM2). [18]
KOJIC ACID DMP84CS Investigative KOJIC ACID increases the expression of PDZ and LIM domain protein 2 (PDLIM2). [24]
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⏷ Show the Full List of 11 Drug(s)
3 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 PDZ and LIM domain protein 2 (PDLIM2). [21]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of PDZ and LIM domain protein 2 (PDLIM2). [23]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of PDZ and LIM domain protein 2 (PDLIM2). [23]
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References

1 PDLIM2 suppression efficiently reduces tumor growth and invasiveness of human castration-resistant prostate cancer-like cells.Prostate. 2016 Feb 15;76(3):273-85. doi: 10.1002/pros.23118. Epub 2015 Oct 26.
2 PDLIM2 suppresses human T-cell leukemia virus type I Tax-mediated tumorigenesis by targeting Tax into the nuclear matrix for proteasomal degradation.Blood. 2009 Apr 30;113(18):4370-80. doi: 10.1182/blood-2008-10-185660. Epub 2009 Jan 8.
3 Pull-down Assay on Streptavidin Beads and Surface Plasmon Resonance Chips for SWATH-MS-based Interactomics.Cancer Genomics Proteomics. 2018 Sep-Oct;15(5):395-404. doi: 10.21873/cgp.20098.
4 Inactivation of the putative ubiquitin-E3 ligase PDLIM2 in classical Hodgkin and anaplastic large cell lymphoma.Leukemia. 2017 Mar;31(3):602-613. doi: 10.1038/leu.2016.238. Epub 2016 Aug 19.
5 PDLIM2 inhibits T helper 17 cell development and granulomatous inflammation through degradation of STAT3.Sci Signal. 2011 Dec 6;4(202):ra85. doi: 10.1126/scisignal.2001637.
6 Construction of a recombinant eukaryotic expression plasmid containing human PDLIM2 gene and its biological activity.Plasmid. 2011 Jul;66(2):106-11. doi: 10.1016/j.plasmid.2011.06.005. Epub 2011 Jul 19.
7 A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NFB and STAT3 in colorectal cancer cells.Gastroenterology. 2014 Oct;147(4):847-859.e11. doi: 10.1053/j.gastro.2014.06.006. Epub 2014 Jun 12.
8 Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.Oncotarget. 2016 Jan 12;7(2):1408-20. doi: 10.18632/oncotarget.6368.
9 Systematic profiling identifies PDLIM2 as a novel prognostic predictor for oesophageal squamous cell carcinoma (ESCC).J Cell Mol Med. 2019 Aug;23(8):5751-5761. doi: 10.1111/jcmm.14491. Epub 2019 Jun 20.
10 Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance.Nat Commun. 2019 Nov 22;10(1):5324. doi: 10.1038/s41467-019-13331-x.
11 Global Proteome and Phospho-proteome Analysis of Merlin-deficient Meningioma and Schwannoma Identifies PDLIM2 as a Novel Therapeutic Target.EBioMedicine. 2017 Feb;16:76-86. doi: 10.1016/j.ebiom.2017.01.020. Epub 2017 Jan 18.
12 PDLIM2 Is a Marker of Adhesion and -Catenin Activity in Triple-Negative Breast Cancer.Cancer Res. 2019 May 15;79(10):2619-2633. doi: 10.1158/0008-5472.CAN-18-2787. Epub 2019 Mar 18.
13 Pdlim2 is a novel actin-regulating protein of podocyte foot processes.Kidney Int. 2011 Nov;80(10):1045-54. doi: 10.1038/ki.2011.231. Epub 2011 Aug 3.
14 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
15 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
16 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
17 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
18 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
19 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
20 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.
21 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.
22 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.
23 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
24 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.