Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT35ZL74)

• DOT Name: Calcium/calmodulin-dependent protein kinase type 1B (PNCK)
• Synonyms: EC 2.7.11.17; CaM kinase I beta; CaM kinase IB; CaM-KI beta; CaMKI-beta; Pregnancy up-regulated non-ubiquitously-expressed CaM kinase
• Gene Name: PNCK
• Related Disease:
  Breast cancer
  Clear cell renal carcinoma
• UniProt ID: KCC1B_HUMAN
• EC Number: 2.7.11.17
• Pfam ID: PF00069
• Sequence:
  MLLLKKHTEDISSVYEIRERLGSGAFSEVVLAQERGSAHLVALKCIPKKALRGKEALVEN
  EIAVLRRISHPNIVALEDVHESPSHLYLAMELVTGGELFDRIMERGSYTEKDASHLVGQV
  LGAVSYLHSLGIVHRDLKPENLLYATPFEDSKIMVSDFGLSKIQAGNMLGTACGTPGYVA
  PELLEQKPYGKAVDVWALGVISYILLCGYPPFYDESDPELFSQILRASYEFDSPFWDDIS
  ESAKDFIRHLLERDPQKRFTCQQALRHLWISGDTAFDRDILGSVSEQIRKNFARTHWKRA
  FNATSFLRHIRKLGQIPEGEGASEQGMARHSHSGLRAGQPPKW
• Function: Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates CREB1 and SYN1/synapsin I. Phosphorylates and activates CAMK1.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[2]

2 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 Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Calcium/calmodulin-dependent protein kinase type 1B (PNCK).	[9]

References

• [1] The caM kinase, Pnck, is spatially and temporally regulated during murine mammary gland development and may identify an epithelial cell subtype involved in breast cancer.Cancer Res. 2000 Oct 1;60(19):5571-7.
• [2] Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma.PLoS One. 2010 Dec 30;5(12):e15224. doi: 10.1371/journal.pone.0015224.
• [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] 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.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] 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.
• [7] 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.
• [8] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.