Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNCD0D0)

• DOT Name: SREBP regulating gene protein (SPRING1)
• Synonyms: SREBF pathway regulator in Golgi 1
• Gene Name: SPRING1
• UniProt ID: SPRNG_HUMAN
• Pfam ID: PF10218
• Sequence:
  MVNLAAMVWRRLLRKRWVLALVFGLSLVYFLSSTFKQEERAVRDRNLLQVHDHNQPIPWK
  VQFNLGNSSRPSNQCRNSIQGKHLITDELGYVCERKDLLVNGCCNVNVPSTKQYCCDGCW
  PNGCCSAYEYCVSCCLQPNKQLLLERFLNRAAVAFQNLFMAVEDHFELCLAKCRTSSQSV
  QHENTYRDPIAKYCYGESPPELFPA
• Function: Positively regulates hepatic SREBP signaling pathway by modulating the proper localization of SCAP (SREBP cleavage-activating protein) to the endoplasmic reticulum, thereby controlling the level of functional SCAP.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of SREBP regulating gene protein (SPRING1).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of SREBP regulating gene protein (SPRING1).	[2]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of SREBP regulating gene protein (SPRING1).	[2]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SREBP regulating gene protein (SPRING1).	[3]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of SREBP regulating gene protein (SPRING1).	[5]

1 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 SREBP regulating gene protein (SPRING1).	[4]

References

• [1] 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.
• [2] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [3] 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.
• [4] 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.
• [5] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.