Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4F9S70)

• DOT Name: G protein-coupled receptor associated sorting protein 3 (GPRASP3)
• Synonyms: Protein BHLHb9; bHLHb9; Transcription regulator of 60 kDa; p60TRP
• Gene Name: GPRASP3
• UniProt ID: GASP3_HUMAN
• Pfam ID: PF04826
• Sequence:
  MAGTKNKTRAQAKTEKKAAIQAKAGAEREATGVVRPVAKTRAKAKAKTGSKTDAVAEMKA
  VSKNKVVAETKEGALSEPKTLGKAMGDFTPKAGNESTSSTCKNEAGTDAWFWAGEEATIN
  SWFWNGEEAGNSFSTKNDKPEIGAQVCAEELEPAAGADCKPRSGAEEEEEENVIGNWFWE
  GDDTSFDPNPKPVSRIVKPQPVYEINEKNRPKDWSEVTIWPNAPAVTPAVLGFRSQAPSE
  ASPPSYIVLASAEENACSLPVATACRPSRNTRSCSQPIPECRFDSDPCIQTIDEIRRQIR
  IREVNGIKPFACPCKMECYMDSEEFEKLVSLLKSTTDPLIHKIARIAMGVHNVHPFAQEF
  INEVGVVTLIESLLSFPSPEMRKKTVITLNPPSGDERQRKIELHVKHMCKETMSFPLNSP
  GQQSGLKILGQLTTDFVHHYIVANYFSELFHLLSSGNCKTRNLVLKLLLNMSENPTAARD
  MINMKALAALKLIFNQKEAKANLVSGVAIFINIKEHIRKGSIVVVDHLSYNTLMAIFREV
  KEIIETM
• Function: Survival and differentiation promoting protein that plays a role in the regulation of neurosynaptogenesis. Induces phosphatase PP2A activity which results in APP dephosphorylation and inhibits BACE1-mediated processing of APP.
• Tissue Specificity: Highly expressed in brain. Not expressed in lung or liver. Down-regulated in brain from patients suffering from Alzheimer disease.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of G protein-coupled receptor associated sorting protein 3 (GPRASP3).	[8]

References

• [1] 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.
• [2] 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.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.