Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT61CSU7)

• DOT Name: Tyrosine-protein kinase STYK1 (STYK1)
• Synonyms: EC 2.7.10.2; Novel oncogene with kinase domain; Protein PK-unique; Serine/threonine/tyrosine kinase 1
• Gene Name: STYK1
• UniProt ID: STYK1_HUMAN
• EC Number: 2.7.10.2
• Pfam ID: PF07714
• Sequence:
  MGMTRMLLECSLSDKLCVIQEKQYEVIIVPTLLVTIFLILLGVILWLFIREQRTQQQRSG
  PQGIAPVPPPRDLSWEAGHGGNVALPLKETSVENFLGATTPALAKLQVPREQLSEVLEQI
  CSGSCGPIFRANMNTGDPSKPKSVILKALKEPAGLHEVQDFLGRIQFHQYLGKHKNLVQL
  EGCCTEKLPLYMVLEDVAQGDLLSFLWTCRRDVMTMDGLLYDLTEKQVYHIGKQVLLALE
  FLQEKHLFHGDVAARNILMQSDLTAKLCGLGLAYEVYTRGAISSTQTIPLKWLAPERLLL
  RPASIRADVWSFGILLYEMVTLGAPPYPEVPPTSILEHLQRRKIMKRPSSCTHTMYSIMK
  SCWRWREADRPSPRELRLRLEAAIKTADDEAVLQVPELVVPELYAAVAGIRVESLFYNYS
  ML
• Function: Probable tyrosine protein-kinase, which has strong transforming capabilities on a variety of cell lines. When overexpressed, it can also induce tumor cell invasion as well as metastasis in distant organs. May act by activating both MAP kinase and phosphatidylinositol 3'-kinases (PI3K) pathways.
• Tissue Specificity: Widely expressed. Highly expressed in brain, placenta and prostate. Expressed in tumor cells such as hepatoma cells L-02, cervix carcinoma cells HeLa, ovary cancer cells Ho8910 and chronic myelogenous leukemia cells K-562, but not in other tumor cells such as epidermoid carcinoma (A-431). Undetectable in most normal lung tissues, widely expressed in lung cancers.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Tyrosine-protein kinase STYK1 (STYK1).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[2]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Tyrosine-protein kinase STYK1 (STYK1).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[4]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tyrosine-protein kinase STYK1 (STYK1).	[10]

References

• [1] 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.
• [2] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [3] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [4] 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.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.