Details of Drug Off-Target (DOT)

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

• DOT Name: Store-operated calcium entry regulator STIMATE (STIMATE)
• Synonyms: STIM-activating enhancer encoded by TMEM110; Transmembrane protein 110
• Gene Name: STIMATE
• Related Disease: Anxiety
• UniProt ID: STIMA_HUMAN
• Pfam ID: PF12400
• Sequence:
  MQGPAGNASRGLPGGPPSTVASGAGRCESGALMHSFGIFLQGLLGVVAFSTLMLKRFREP
  KHERRPWRIWFLDTSKQAIGMLFIHFANVYLADLTEEDPCSLYLINFLLDATVGMLLIYV
  GVRAVSVLVEWQQWESLRFGEYGDPLQCGAWVGQCALYIVIMIFEKSVVFIVLLILQWKK
  VALLNPIENPDLKLAIVMLIVPFFVNALMFWVVDNFLMRKGKTKAKLEERGANQDSRNGS
  KVRYRRAASHEESESEILISADDEMEESDVEEDLRRLTPLKPVKKKKHRFGLPV
• Function: Acts as a regulator of store-operated Ca(2+) entry (SOCE) at junctional sites that connect the endoplasmic reticulum (ER) and plasma membrane (PM), called ER-plasma membrane (ER-PM) junction or cortical ER. SOCE is a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts by interacting with STIM1, promoting STIM1 conformational switch. Involved in STIM1 relocalization to ER-PM junctions. Contributes to the maintenance and reorganization of store-dependent ER-PM junctions.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety	DISIJDBA	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Store-operated calcium entry regulator STIMATE (STIMATE).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Store-operated calcium entry regulator STIMATE (STIMATE).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Store-operated calcium entry regulator STIMATE (STIMATE).	[2]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Store-operated calcium entry regulator STIMATE (STIMATE).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Store-operated calcium entry regulator STIMATE (STIMATE).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Store-operated calcium entry regulator STIMATE (STIMATE).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Store-operated calcium entry regulator STIMATE (STIMATE).	[4]

References

• [1] Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [6] 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.