Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVXQC81)

• DOT Name: PDZ and LIM domain protein 3 (PDLIM3)
• Synonyms: Actinin-associated LIM protein; Alpha-actinin-2-associated LIM protein
• Gene Name: PDLIM3
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
  Acute liver failure
  Ankylosing spondylitis
  Bone disease
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cholestasis
  Choriocarcinoma
  Chromosomal disorder
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Dilated cardiomyopathy 1A
  facioscapulohumeral muscular dystrophy
  Fatty liver disease
  Germ cell tumor
  Hematologic disease
  Hepatocellular carcinoma
  Hypercalcaemia
  Hyperlipidemia
  Isolated cleft palate
  Kidney failure
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Non-alcoholic fatty liver disease
  Prostate cancer
  Prostate carcinoma
  Pyropoikilocytosis, hereditary
  Renal cell carcinoma
  Sjogren syndrome
  Amyotrophic lateral sclerosis
  Hepatitis C virus infection
  Rheumatoid arthritis
  Acute myelogenous leukaemia
  Alzheimer disease
  Dilated cardiomyopathy
  Huntington disease
  Non-hodgkin lymphoma
  Bone osteosarcoma
  Congenital contractural arachnodactyly
  Familial hypocalciuric hypercalcemia 1
  Hypertrophic cardiomyopathy
  Hypophosphatasia
  Neoplasm
  Osteoporosis
  Osteosarcoma
• UniProt ID: PDLI3_HUMAN
• Pfam ID: PF15936 ; PF00412 ; PF00595
• Sequence:
  MPQTVILPGPAPWGFRLSGGIDFNQPLVITRITPGSKAAAANLCPGDVILAIDGFGTESM
  THADAQDRIKAAAHQLCLKIDRGETHLWSPQVSEDGKAHPFKINLESEPQDGNYFEHKHN
  IRPKPFVIPGRSSGCSTPSGIDCGSGRSTPSSVSTVSTICPGDLKVAAKLAPNIPLEMEL
  PGVKIVHAQFNTPMQLYSDDNIMETLQGQVSTALGETPLMSEPTASVPPESDVYRMLHDN
  RNEPTQPRQSGSFRVLQGMVDDGSDDRPAGTRSVRAPVTKVHGGSGGAQRMPLCDKCGSG
  IVGAVVKARDKYRHPECFVCADCNLNLKQKGYFFIEGELYCETHARARTKPPEGYDTVTL
  YPKA
• Function: May play a role in the organization of actin filament arrays within muscle cells.
• Tissue Specificity: Isoform 1 is highly expressed in differentiated skeletal muscle. Isoform 2 is heart-specific.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]
Acute liver failure	DIS5EZKX	Strong	Genetic Variation	[2]
Ankylosing spondylitis	DISRC6IR	Strong	Altered Expression	[3]
Bone disease	DISE1F82	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[6]
Cholestasis	DISDJJWE	Strong	Biomarker	[7]
Choriocarcinoma	DISDBVNL	Strong	Biomarker	[8]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[11]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[12]
facioscapulohumeral muscular dystrophy	DISSE0H0	Strong	Altered Expression	[13]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[14]
Germ cell tumor	DIS62070	Strong	Altered Expression	[8]
Hematologic disease	DIS9XD9A	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[15]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[16]
Hyperlipidemia	DIS61J3S	Strong	Altered Expression	[17]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[18]
Kidney failure	DISOVQ9P	Strong	Biomarker	[19]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[20]
Lung cancer	DISCM4YA	Strong	Biomarker	[21]
Lung carcinoma	DISTR26C	Strong	Biomarker	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Pyropoikilocytosis, hereditary	DISZGN3B	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[10]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[25]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[26]
Hepatitis C virus infection	DISQ0M8R	moderate	Genetic Variation	[27]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[28]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Genetic Variation	[29]
Alzheimer disease	DISF8S70	Disputed	Biomarker	[26]
Dilated cardiomyopathy	DISX608J	Disputed	Autosomal dominant	[30]
Huntington disease	DISQPLA4	Disputed	Biomarker	[26]
Non-hodgkin lymphoma	DISS2Y8A	Disputed	Genetic Variation	[29]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[31]
Congenital contractural arachnodactyly	DISOM1K7	Limited	Biomarker	[32]
Familial hypocalciuric hypercalcemia 1	DISPW6O5	Limited	Genetic Variation	[33]
Hypertrophic cardiomyopathy	DISQG2AI	Limited	Autosomal dominant	[30]
Hypophosphatasia	DISCQ0O2	Limited	Biomarker	[34]
Neoplasm	DISZKGEW	Limited	Altered Expression	[35]
Osteoporosis	DISF2JE0	Limited	Altered Expression	[36]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of PDZ and LIM domain protein 3 (PDLIM3).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[42]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[44]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of PDZ and LIM domain protein 3 (PDLIM3).	[41]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[45]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[46]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[47]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[48]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of PDZ and LIM domain protein 3 (PDLIM3).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PDZ and LIM domain protein 3 (PDLIM3).	[51]

1 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 PDZ and LIM domain protein 3 (PDLIM3).	[43]

References

• [1] Point-of-Care Assay of Alkaline Phosphatase Enzymatic Activity Using a Thermometer or Temperature Discoloration Sticker as Readout.Anal Chem. 2019 Jun 18;91(12):7943-7949. doi: 10.1021/acs.analchem.9b01883. Epub 2019 May 31.
• [2] Outcomes of Acute Liver Injury in Adults Due to Wilson's Disease: Is Survival Without Transplant Possible?.Liver Transpl. 2020 Mar;26(3):330-336. doi: 10.1002/lt.25703.
• [3] Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis.Int J Rheum Dis. 2019 Feb;22(2):252-261. doi: 10.1111/1756-185X.13419. Epub 2018 Nov 11.
• [4] Amifostine Suppresses the Side Effects of Radiation on BMSCs by Promoting Cell Proliferation and Reducing ROS Production.Stem Cells Int. 2019 Jan 9;2019:8749090. doi: 10.1155/2019/8749090. eCollection 2019.
• [5] Three gold indicators for breast cancer prognosis: a case-control study with ROC analysis for novel ratios related to CBC with (ALP and LDH).Mol Biol Rep. 2019 Apr;46(2):2013-2027. doi: 10.1007/s11033-019-04650-9. Epub 2019 Jan 31.
• [6] Pharmacodynamic effects of Dan-hong injection in rats with blood stasis syndrome.Biomed Pharmacother. 2019 Oct;118:109187. doi: 10.1016/j.biopha.2019.109187. Epub 2019 Jul 11.
• [7] Paeoniflorin attenuates ANIT-induced cholestasis by inhibiting apoptosis in vivo via mitochondria-dependent pathway.Biomed Pharmacother. 2017 May;89:696-704. doi: 10.1016/j.biopha.2017.02.084. Epub 2017 Mar 6.
• [8] Expression of the germ cell alkaline phosphatase gene in human choriocarcinoma cells.J Biol Chem. 1989 Jul 25;264(21):12611-9.
• [9] Granulocytes' enzymes as biomarkers of radiotoxicity in individuals occupationally exposed to low-level radiation.J BUON. 2009 Jan-Mar;14(1):85-91.
• [10] Reduced L/B/K alkaline phosphatase gene expression in renal cell carcinoma: plausible role in tumorigenesis.Biochimie. 2014 Sep;104:27-35. doi: 10.1016/j.biochi.2014.05.011. Epub 2014 Jun 5.
• [11] The intestinal epithelial cell differentiation marker intestinal alkaline phosphatase (ALPi) is selectively induced by histone deacetylase inhibitors (HDACi) in colon cancer cells in a Kruppel-like factor 5 (KLF5)-dependent manner.J Biol Chem. 2014 Sep 5;289(36):25306-16. doi: 10.1074/jbc.M114.557546. Epub 2014 Jul 18.
• [12] Novel polymorphisms in PDLIM3 and PDLIM5 gene encoding Z-line proteins increase risk of idiopathic dilated cardiomyopathy.J Cell Mol Med. 2019 Oct;23(10):7054-7062. doi: 10.1111/jcmm.14607. Epub 2019 Aug 19.
• [13] Actinin-associated LIM protein-deficient mice maintain normal development and structure of skeletal muscle.Mol Cell Biol. 2001 Mar;21(5):1682-7. doi: 10.1128/MCB.21.5.1682-1687.2001.
• [14] Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis.Free Radic Res. 2019 May;53(5):486-496. doi: 10.1080/10715762.2019.1608982. Epub 2019 May 7.
• [15] Hypersplenism is correlated with increased risk of hepatocellular carcinoma in patients with post-hepatitis cirrhosis.Tumour Biol. 2016 Jul;37(7):8889-900. doi: 10.1007/s13277-015-4764-5. Epub 2016 Jan 11.
• [16] The chloride/phosphate ratio combined with alkaline phosphatase as a valuable predictive marker for primary hyperparathyroidism in Chinese individuals.Sci Rep. 2017 Jul 7;7(1):4868. doi: 10.1038/s41598-017-05183-6.
• [17] Anti-hyperlipidemic and antioxidant effects of alkali-extractable mycelia polysaccharides by Pleurotus eryngii var. tuolensis.Carbohydr Polym. 2017 Nov 1;175:282-292. doi: 10.1016/j.carbpol.2017.08.009. Epub 2017 Aug 3.
• [18] Oral administration of Nigella sativa oil and thymoquinone attenuates long term cisplatin treatment induced toxicity and oxidative damage in rat kidney.Biomed Pharmacother. 2017 Dec;96:912-923. doi: 10.1016/j.biopha.2017.12.007. Epub 2017 Dec 7.
• [19] Rat liver and kidney post-mitochondrial dysfunction by addition of chronic mixed metal intoxication and hepatorenal wellness mediated by phenolic components from Croton zambiscus leaves.Environ Toxicol Pharmacol. 2020 Feb;74:103293. doi: 10.1016/j.etap.2019.103293. Epub 2019 Nov 9.
• [20] Risk of endoscopic biliary interventions in primary sclerosing cholangitis is similar between patients with and without cirrhosis.PLoS One. 2018 Aug 20;13(8):e0202686. doi: 10.1371/journal.pone.0202686. eCollection 2018.
• [21] Bone turnover markers and novel biomarkers in lung cancer bone metastases.Biomarkers. 2018 Sep;23(6):518-526. doi: 10.1080/1354750X.2018.1463566. Epub 2018 Apr 23.
• [22] Chicory (Cichorium intybus L.) polysaccharides attenuate high-fat diet induced non-alcoholic fatty liver disease via AMPK activation.Int J Biol Macromol. 2018 Oct 15;118(Pt A):886-895. doi: 10.1016/j.ijbiomac.2018.06.140. Epub 2018 Jun 28.
• [23] Bufalin suppresses the migration and invasion of prostate cancer cells through HOTAIR, the sponge of miR-520b.Acta Pharmacol Sin. 2019 Sep;40(9):1228-1236. doi: 10.1038/s41401-019-0234-8. Epub 2019 Apr 26.
• [24] Tissue non-specific alkaline phosphatase activity and mineralization capacity of bi-allelic mutations from severe perinatal and asymptomatic hypophosphatasia phenotypes: Results from an in vitro mutagenesis model.Bone. 2019 Oct;127:9-16. doi: 10.1016/j.bone.2019.05.031. Epub 2019 May 27.
• [25] Th17/Treg cell level and clinical characteristics of peripheral blood of patients with Sjogren's syndrome complicated with primary biliary cirrhosis.Medicine (Baltimore). 2019 Jun;98(24):e15952. doi: 10.1097/MD.0000000000015952.
• [26] The cargo receptor SQSTM1 ameliorates neurofibrillary tangle pathology and spreading through selective targeting of pathological MAPT (microtubule associated protein tau).Autophagy. 2019 Apr;15(4):583-598. doi: 10.1080/15548627.2018.1532258. Epub 2018 Oct 16.
• [27] Effect of IL15 rs10833 and SCARB1 rs10846744 on virologic responses in chronic hepatitis C patients treated with pegylated interferon- and ribavirin.Gene. 2017 Sep 30;630:28-34. doi: 10.1016/j.gene.2017.08.005. Epub 2017 Aug 4.
• [28] Rosmarinic acid exerts an antagonistic effect on vascular calcification by regulating the Nrf2 signalling pathway.Free Radic Res. 2019 Feb;53(2):187-197. doi: 10.1080/10715762.2018.1558447. Epub 2019 Mar 13.
• [29] A case of angioimmunoblastic T-cell non-Hodgkin lymphoma with a neocentric inv dup(1).Cancer Genet Cytogenet. 2010 Oct 1;202(1):38-42. doi: 10.1016/j.cancergencyto.2010.06.004.
• [30] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [31] Lung cells support osteosarcoma cell migration and survival.BMC Cancer. 2017 Jan 25;17(1):78. doi: 10.1186/s12885-017-3047-5.
• [32] Surveillance of primary sclerosing cholangitis with ERC and brush cytology: risk factors for cholangiocarcinoma.Scand J Gastroenterol. 2017 Feb;52(2):242-249. doi: 10.1080/00365521.2016.1250281. Epub 2016 Nov 3.
• [33] Association between iron overload and osteoporosis in patients with hereditary hemochromatosis.Osteoporos Int. 2009 Apr;20(4):549-55. doi: 10.1007/s00198-008-0701-4. Epub 2008 Jul 26.
• [34] HYPOPHOSPHATASIA: CLINICAL ASSESSMENT AND MANAGEMENT IN THE ADULT PATIENT-A NARRATIVE REVIEW.Endocr Pract. 2018 Dec;24(12):1086-1092. doi: 10.4158/EP-2018-0194. Epub 2018 Oct 5.
• [35] The effects of PTBP3 silencing on the proliferation and differentiation of MKN45 human gastric cancer cells.Life Sci. 2014 Sep 26;114(1):29-35. doi: 10.1016/j.lfs.2014.07.038. Epub 2014 Aug 10.
• [36] LncRNA NEAT1/miR-29b-3p/BMP1 axis promotes osteogenic differentiation in human bone marrow-derived mesenchymal stem cells.Pathol Res Pract. 2019 Mar;215(3):525-531. doi: 10.1016/j.prp.2018.12.034. Epub 2018 Dec 31.
• [37] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [38] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [39] Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes. Arch Toxicol. 2018 Jan;92(1):371-381.
• [40] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [41] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [42] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [43] 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.
• [44] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [45] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [46] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [47] 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.
• [48] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [49] 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.
• [50] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [51] 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.