Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLGUM8H)

• DOT Name: Paladin (PALD1)
• Gene Name: PALD1
• Related Disease:
  Adenocarcinoma
  Pancreatic tumour
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Diabetic kidney disease
  Matthew-Wood syndrome
  Neoplasm
  Nephropathy
  Non-insulin dependent diabetes
  Pancreatic cancer
  Vasculitis
  Pulmonary emphysema
  Familial pancreatic carcinoma
  Patent ductus arteriosus
• UniProt ID: PALD_HUMAN
• Pfam ID: PF14566
• Sequence:
  MGTTASTAQQTVSAGTPFEGLQGSGTMDSRHSVSIHSFQSTSLHNSKAKSIIPNKVAPVV
  ITYNCKEEFQIHDELLKAHYTLGRLSDNTPEHYLVQGRYFLVRDVTEKMDVLGTVGSCGA
  PNFRQVQGGLTVFGMGQPSLSGFRRVLQKLQKDGHRECVIFCVREEPVLFLRADEDFVSY
  TPRDKQNLHENLQGLGPGVRVESLELAIRKEIHDFAQLSENTYHVYHNTEDLWGEPHAVA
  IHGEDDLHVTEEVYKRPLFLQPTYRYHRLPLPEQGSPLEAQLDAFVSVLRETPSLLQLRD
  AHGPPPALVFSCQMGVGRTNLGMVLGTLILLHRSGTTSQPEAAPTQAKPLPMEQFQVIQS
  FLRMVPQGRRMVEEVDRAITACAELHDLKEVVLENQKKLEGIRPESPAQGSGSRHSVWQR
  ALWSLERYFYLILFNYYLHEQYPLAFALSFSRWLCAHPELYRLPVTLSSAGPVAPRDLIA
  RGSLREDDLVSPDALSTVREMDVANFRRVPRMPIYGTAQPSAKALGSILAYLTDAKRRLR
  KVVWVSLREEAVLECDGHTYSLRWPGPPVAPDQLETLEAQLKAHLSEPPPGKEGPLTYRF
  QTCLTMQEVFSQHRRACPGLTYHRIPMPDFCAPREEDFDQLLEALRAALSKDPGTGFVFS
  CLSGQGRTTTAMVVAVLAFWHIQGFPEVGEEELVSVPDAKFTKGEFQVVMKVVQLLPDGH
  RVKKEVDAALDTVSETMTPMHYHLREIIICTYRQAKAAKEAQEMRRLQLRSLQYLERYVC
  LILFNAYLHLEKADSWQRPFSTWMQEVASKAGIYEILNELGFPELESGEDQPFSRLRYRW
  QEQSCSLEPSAPEDLL
• Tissue Specificity: Expressed in endothelial cells, and in certain larger vessels, in mural cells. In the brain, possibly expressed in microglia. Expressed in peripheral blood mononuclear cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Pancreatic tumour	DIS3U0LK	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[3]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Diabetic kidney disease	DISJMWEY	Strong	Altered Expression	[6]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Nephropathy	DISXWP4P	Strong	Altered Expression	[8]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[9]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[10]
Vasculitis	DISQRKDX	Strong	Altered Expression	[8]
Pulmonary emphysema	DIS5M7HZ	moderate	Biomarker	[11]
Familial pancreatic carcinoma	DIS1XROR	Limited	Genetic Variation	[12]
Patent ductus arteriosus	DIS9P8YS	Limited	Biomarker	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Paladin (PALD1).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Paladin (PALD1).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Paladin (PALD1).	[16]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Paladin (PALD1).	[17]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Paladin (PALD1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Paladin (PALD1).	[19]

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 affects the methylation of Paladin (PALD1).	[18]

References

• [1] Palladin expression is a conserved characteristic of the desmoplastic tumor microenvironment and contributes to altered gene expression.Cytoskeleton (Hoboken). 2015 Aug;72(8):402-11. doi: 10.1002/cm.21239. Epub 2015 Sep 3.
• [2] Twist1-induced activation of human fibroblasts promotes matrix stiffness by upregulating palladin and collagen 1(VI).Oncogene. 2016 Oct 6;35(40):5224-5236. doi: 10.1038/onc.2016.57. Epub 2016 Mar 14.
• [3] Polymorphism of the palladin gene and cardiovascular outcome in patients with atherosclerosis.Eur J Clin Invest. 2011 Apr;41(4):365-71. doi: 10.1111/j.1365-2362.2010.02416.x. Epub 2010 Nov 4.
• [4] Akt isoform-specific signaling in breast cancer: uncovering an anti-migratory role for palladin.Cell Adh Migr. 2011 May-Jun;5(3):211-4. doi: 10.4161/cam.5.3.15790. Epub 2011 May 1.
• [5] Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells.Int J Oncol. 2010 Oct;37(4):909-26. doi: 10.3892/ijo_00000742.
• [6] The Role of Palladin in Podocytes.J Am Soc Nephrol. 2018 Jun;29(6):1662-1678. doi: 10.1681/ASN.2017091039. Epub 2018 May 2.
• [7] The role of stromal cancer-associated fibroblasts in pancreatic cancer.J Hematol Oncol. 2017 Mar 28;10(1):76. doi: 10.1186/s13045-017-0448-5.
• [8] Palladin is upregulated in kidney disease and contributes to epithelial cell migration after injury.Sci Rep. 2015 Jan 9;5:7695. doi: 10.1038/srep07695.
• [9] Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population.Gene. 2018 Nov 30;677:324-331. doi: 10.1016/j.gene.2018.08.041. Epub 2018 Aug 18.
• [10] Screening of high-risk families for pancreatic cancer.Pancreatology. 2009;9(3):215-22. doi: 10.1159/000210262. Epub 2009 Apr 7.
• [11] Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema.Sci Rep. 2017 Nov 13;7(1):15453. doi: 10.1038/s41598-017-14894-9.
• [12] Absence of deleterious palladin mutations in patients with familial pancreatic cancer.Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1328-30. doi: 10.1158/1055-9965.EPI-09-0056. Epub 2009 Mar 31.
• [13] Isoform-specific upregulation of palladin in human and murine pancreas tumors.PLoS One. 2010 Apr 26;5(4):e10347. doi: 10.1371/journal.pone.0010347.
• [14] 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.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] 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.
• [17] 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.
• [18] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [19] 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.