Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZNWS4)

• DOT Name: Jerky protein homolog-like (JRKL)
• Synonyms: Human homolog of mouse jerky gene protein; HHMJG
• Gene Name: JRKL
• UniProt ID: JERKL_HUMAN
• Pfam ID: PF04218 ; PF03184 ; PF03221
• Sequence:
  MSGKRKRVVLTIKDKLDIIKKLEDGGSSKQLAVIYGIGETTVRDIRKNKEKIITYASSSD
  STSLLAKRKSMKPSMYEELDRAMLEWFNQQRAKGNPISGPICAKRAEFFFYALGMDGDFN
  PSAGWLTRFKQRHSIREINIRNERLNGDETAVEDFCNNFRDFIERENLQPEQIYNADETG
  LFWKCLPSRISVIKGKCTVPGHKSIEERVTIMCCANATGLHKLKLCVVGKAKKPRSFKST
  DTLNLPVSYFSQKGAWMDLSIFRQWFDKIFVPQVREYLRSKGLQEKAVLLLDNSPTHPNE
  NVLRSDDGQIFAKYLPPNVASLIQPSDQGVIATMKRNYRAGLLQNNLEEGNDLKSFWKKL
  TLLDALYEIAMAWNLVKPVTISRAWKKILPMVEEKESLDFDVEDISVATVAAILQHTKGL
  ENVTTENLEKWLEVDSTEPGYEVLTDSEIIRRAQGQADESSENEEEEIELIPEKHINHAA
  ALQWTENLLDYLEQQGDMILPDRLVIRKLRATIRNKQKMTKSSQ
• Tissue Specificity: Abundantly expressed in the majority of tissues examined, including brain and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

8 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 Jerky protein homolog-like (JRKL).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Jerky protein homolog-like (JRKL).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Jerky protein homolog-like (JRKL).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Jerky protein homolog-like (JRKL).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Jerky protein homolog-like (JRKL).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Jerky protein homolog-like (JRKL).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Jerky protein homolog-like (JRKL).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Jerky protein homolog-like (JRKL).	[9]

2 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 increases the methylation of Jerky protein homolog-like (JRKL).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Jerky protein homolog-like (JRKL).	[10]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [8] 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.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.