Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1AAYWO)

• DOT Name: Junctional sarcoplasmic reticulum protein 1 (JSRP1)
• Synonyms: Junctional-face membrane protein of 45 kDa homolog; JP-45
• Gene Name: JSRP1
• Related Disease:
  Graves disease
  Neuromuscular disease
  Polycystic ovarian syndrome
• UniProt ID: JSPR1_HUMAN
• Pfam ID: PF15312
• Sequence:
  MSMTTRAWEELDGGLGSCQALEDHSALAETQEDRASATPRLADSGSVPHDSQVAEGPSVD
  TRPKKMEKEPAARGTPGTGKERLKAGASPRSVPARKKAQTAPPLQPPPPPPALSEELPWG
  DLSLNKCLVLASLVALLGSAFQLCRDAVPGEAALQARVPEPWVPPSSAPREPSSPLPKFE
  AQAPPSAPPAPRAEAEVRPKIPGSREAAENDEEEPGEATGEAVREDRVTLADRGPKERPR
  REGKPRKEKPRKEERPKKERPRKEERPRAAREPREALPQRWESREGGHRPWARDSRDAEP
  RKKQAWVSPRRPDEEQRPGSRQKLRAGKGRD
• Function: Involved in skeletal muscle excitation/contraction coupling (EC), probably acting as a regulator of the voltage-sensitive calcium channel CACNA1S. EC is a physiological process whereby an electrical signal (depolarization of the plasma membrane) is converted into a chemical signal, a calcium gradient, by the opening of ryanodine receptor calcium release channels. May regulate CACNA1S membrane targeting and activity.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Graves disease	DISU4KOQ	Strong	Genetic Variation	[1]
Neuromuscular disease	DISQTIJZ	Strong	Genetic Variation	[2]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[3]

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 Junctional sarcoplasmic reticulum protein 1 (JSRP1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Junctional sarcoplasmic reticulum protein 1 (JSRP1).	[6]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Junctional sarcoplasmic reticulum protein 1 (JSRP1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Junctional sarcoplasmic reticulum protein 1 (JSRP1).	[5]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Junctional sarcoplasmic reticulum protein 1 (JSRP1).	[8]

References

• [1] Follow-up of potential novel Graves' disease susceptibility loci, identified in the UK WTCCC genome-wide nonsynonymous SNP study.Eur J Hum Genet. 2010 Sep;18(9):1021-6. doi: 10.1038/ejhg.2010.55. Epub 2010 May 5.
• [2] JP-45/JSRP1 variants affect skeletal muscle excitation-contraction coupling by decreasing the sensitivity of the dihydropyridine receptor.Hum Mutat. 2013 Jan;34(1):184-90. doi: 10.1002/humu.22209. Epub 2012 Oct 11.
• [3] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [4] 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.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] 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.
• [8] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.