Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV1Y4ON)

• DOT Name: Proline and serine-rich protein 1 (PROSER1)
• Gene Name: PROSER1
• Related Disease:
  Crohn disease
  Ulcerative colitis
• UniProt ID: PRSR1_HUMAN
• Pfam ID: PF14771
• Sequence:
  MDKKSFEMVLDEIRKAVLTEYKLKAIEYVHGYFSSEQVVDLLRYFSWAEPQLKAMKALQH
  KMVAVQPTEVVNILNCFTFSKDKLVALELLASNIIDAQNSRPIEDLFRVNMSEKKRCKRI
  LEQAFKGGCKAPHAMISSCGTIPGNPYPKGRPSRINGIFPGTPLKKDGEECTNEGKGIAA
  RILGPSKPPPSTYNPHKPVPYPIPPCRPHATIAPSAYNNAGLVPLANVIAPPPPPYTPNP
  VGTENEDLSNPSKPIQNQTFSTPASQLFSPHGSNPSTPAATPVPTASPVKAINHPSASAA
  ATVSGMNLLNTVLPVFPGQVSSAVHTPQPSIPNPTVIRTPSLPTAPVTSIHSTTTTPVPS
  IFSGLVSLPGPSATPTAATPTPGPTPRSTLGSSEAFASTSAPFTSLPFSTSSSAASTSNP
  NSASLSSVFAGLPLPLPPTSQGLSNPTPVIAGGSTPSVAGPLGVNSPLLSALKGFLTSND
  TNLINSSALSSAVTSGLASLSSLTLQNSDSSASAPNKCYAPSAIPTPQRTSTPGLALFPG
  LPSPVANSTSTPLTLPVQSPLATAASASTSVPVSCGSSASLLRGPHPGTSDLHISSTPAA
  TTLPVMIKTEPTSPTPSAFKGPSHSGNPSHGTLGLSGTLGRAYTSTSVPISLSACLNPAL
  SGLSSLSTPLNGSNPLSSISLPPHGSSTPIAPVFTALPSFTSLTNNFPLTGNPSLNPSVS
  LPGSLIATSSTAATSTSLPHPSSTAAVLSGLSASAPVSAAPFPLNLSTAVPSLFSVTQGP
  LSSSNPSYPGFSVSNTPSVTPALPSFPGLQAPSTVAAVTPLPVAATAPSPAPVLPGFASA
  FSSNFNSALVAQAGLSSGLQAAGSSVFPGLLSLPGIPGFPQNPSQSSLQELQHNAAAQSA
  LLQQVHSASALESYPAQPDGFPSYPSAPGTPFSLQPSLSQSGWQ
• Function: Mediates OGT interaction with and O-GlcNAcylation of TET2 to control TET2 stabilization at enhancers and CpG islands (CGIs).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Disputed	Genetic Variation	[1]
Ulcerative colitis	DIS8K27O	Disputed	Genetic Variation	[1]

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 Proline and serine-rich protein 1 (PROSER1).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Proline and serine-rich protein 1 (PROSER1).	[8]

7 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 Proline and serine-rich protein 1 (PROSER1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Proline and serine-rich protein 1 (PROSER1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proline and serine-rich protein 1 (PROSER1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Proline and serine-rich protein 1 (PROSER1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Proline and serine-rich protein 1 (PROSER1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Proline and serine-rich protein 1 (PROSER1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Proline and serine-rich protein 1 (PROSER1).	[10]

References

• [1] An SNP linkage scan identifies significant Crohn's disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29.Genes Immun. 2008 Mar;9(2):161-7. doi: 10.1038/sj.gene.6364460. Epub 2008 Jan 31.
• [2] 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.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] 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.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.