Details of Drug Off-Target (DOT)

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

• DOT Name: Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3)
• Synonyms: Ezrin-binding protein PACE-1; SCY1-like protein 3
• Gene Name: SCYL3
• Related Disease: Colorectal carcinoma
• UniProt ID: PACE1_HUMAN
• Pfam ID: PF07714
• Sequence:
  MGSENSALKSYTLREPPFTLPSGLAVYPAVLQDGKFASVFVYKRENEDKVNKAAKHLKTL
  RHPCLLRFLSCTVEADGIHLVTERVQPLEVALETLSSAEVCAGIYDILLALIFLHDRGHL
  THNNVCLSSVFVSEDGHWKLGGMETVCKVSQATPEFLRSIQSIRDPASIPPEEMSPEFTT
  LPECHGHARDAFSFGTLVESLLTILNEQVSADVLSSFQQTLHSTLLNPIPKCRPALCTLL
  SHDFFRNDFLEVVNFLKSLTLKSEEEKTEFFKFLLDRVSCLSEELIASRLVPLLLNQLVF
  AEPVAVKSFLPYLLGPKKDHAQGETPCLLSPALFQSRVIPVLLQLFEVHEEHVRMVLLSH
  IEAYVEHFTQEQLKKVILPQVLLGLRDTSDSIVAITLHSLAVLVSLLGPEVVVGGERTKI
  FKRTAPSFTKNTDLSLEDSPMCVVCSHHSQISPILENPFSSIFPKCFFSGSTPINSKKHI
  QRDYYNTLLQTGDPFSQPIKFPINGLSDVKNTSEDSENFPSSSKKSEEWPDWSEPEEPEN
  QTVNIQIWPREPCDDVKSQCTTLDVEESSWDDCEPSSLDTKVNPGGGITATKPVTSGEQK
  PIPALLSLTEESMPWKSSLPQKISLVQRGDDADQIEPPKVSSQERPLKVPSELGLGEEFT
  IQVKKKPVKDPEMDWFADMIPEIKPSAAFLILPELRTEMVPKKDDVSPVMQFSSKFAAAE
  ITEGEAEGWEEEGELNWEDNNW
• Function: May play a role in regulating cell adhesion/migration complexes in migrating cells.
• Tissue Specificity: Ubiquitously 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
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]

7 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 Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[9]

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 affects the methylation of Protein-associating with the carboxyl-terminal domain of ezrin (SCYL3).	[8]

References

• [1] Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient.Oncotarget. 2017 Jul 24;8(33):55353-55360. doi: 10.18632/oncotarget.19512. eCollection 2017 Aug 15.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.