Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI29LKO)

• DOT Name: Protein SREK1IP1 (SREK1IP1)
• Synonyms: SFRS12-interacting protein 1; SREK1-interacting protein 1; Splicing regulatory protein of 18 kDa; p18SRP
• Gene Name: SREK1IP1
• Related Disease: Alzheimer disease
• UniProt ID: SR1IP_HUMAN
• Pfam ID: PF13917
• Sequence:
  MAVPGCNKDSVRAGCKKCGYPGHLTFECRNFLRVDPKRDIVLDVSSTSSEDSDEENEELN
  KLQALQEKRINEEEEKKKEKSKEKIKLKKKRKRSYSSSSTEEDTSKQKKQKYQKKEKKKE
  KKSKSKKGKHHKKEKKKRKKEKHSSTPNSSEFSRK
• Function: Possible splicing regulator involved in the control of cellular survival.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein SREK1IP1 (SREK1IP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein SREK1IP1 (SREK1IP1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein SREK1IP1 (SREK1IP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein SREK1IP1 (SREK1IP1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein SREK1IP1 (SREK1IP1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein SREK1IP1 (SREK1IP1).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein SREK1IP1 (SREK1IP1).	[8]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein SREK1IP1 (SREK1IP1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein SREK1IP1 (SREK1IP1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein SREK1IP1 (SREK1IP1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein SREK1IP1 (SREK1IP1).	[10]

References

• [1] The splicing regulatory protein p18SRP is down-regulated in Alzheimer's disease brain.J Mol Neurosci. 2004;24(2):269-76. doi: 10.1385/JMN:24:2:269.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [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] 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.
• [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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.