Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW5YPKM)

• DOT Name: Inactive serine/threonine-protein kinase PLK5 (PLK5)
• Synonyms: Polo-like kinase 5; PLK-5
• Gene Name: PLK5
• Related Disease:
  Adult glioblastoma
  Astrocytoma
  Brain cancer
  Brain neoplasm
  Clear cell renal carcinoma
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: PLK5_HUMAN
• Sequence:
  MYTVLTGTPPFMASPLSEMYQNIREGHYPEPAHLSANARRLIVHLLAPNPAERPSLDHLL
  QDDFFTQGFTPDRLPAHSCHSPPIFAIPPPLGRIFRKVGQRLLTQCRPPCPFTPKEASGP
  GEGGPDPDSMEWDGESSLSAKEVPCLEGPIHLVAQGTLQSDLAGPEGSRRPEVEAALRHL
  QLCLDVGPPATQDPLGEQQPILWAPKWVDYSSKYGFGYQLLDGGRTGRHPHGPATPRREG
  TLPTPVPPAGPGLCLLRFLASEHALLLLFSNGMVQVSFSGVPAQLVLSGEGEGLQLTLWE
  QGSPGTSYSLDVPRSHGCAPTTGQHLHHALRMLQSI
• Function: Inactive serine/threonine-protein kinase that plays a role in cell cycle progression and neuronal differentiation.
• Tissue Specificity: Expressed in the brain, neurons and glial cells. Also expressed in highly differentiated cells, such as the serous acini in the parotid gland, distal and proximal tubules of the kidney, tubules of the seminal gland, Kupffer cells and some hepatocytes in the liver, and some cells in the germinal center of lymph nodes (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Astrocytoma	DISL3V18	Strong	Posttranslational Modification	[1]
Brain cancer	DISBKFB7	Strong	Altered Expression	[1]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Strong	Posttranslational Modification	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Inactive serine/threonine-protein kinase PLK5 (PLK5).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Inactive serine/threonine-protein kinase PLK5 (PLK5).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Inactive serine/threonine-protein kinase PLK5 (PLK5).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Inactive serine/threonine-protein kinase PLK5 (PLK5).	[4]

References

• [1] Plk5, a polo box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression.Mol Cell Biol. 2011 Mar;31(6):1225-39. doi: 10.1128/MCB.00607-10. Epub 2011 Jan 18.
• [2] Genetic mutations associated with metastatic clear cell renal cell carcinoma.Oncotarget. 2016 Mar 29;7(13):16172-9. doi: 10.18632/oncotarget.7473.
• [3] 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.
• [4] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.