Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4RVPSU)

• DOT Name: PWWP domain-containing protein 2A (PWWP2A)
• Gene Name: PWWP2A
• UniProt ID: PWP2A_HUMAN
• Pfam ID: PF00855
• Sequence:
  MAAVAAEAAATAASPGEGGAGEAEPEMEPIPGSEAGTDPLPVTATEASVPDGETDGQQSA
  PQADEPPLPPPPPPPGELARSPEAVGPELEAEEKLSVRVAESAAAAPQGGPELPPSPASP
  PEQPPAPEEREEPPLPQPVAPALVPPAGGDSTVSQLIPGSEVRVTLDHIIEDALVVSFRF
  GEKLFSGVLMDLSKRFGPHGIPVTVFPKREYKDKPEAMPLQSNTFQEGTEVKCEANGAVP
  DDPSPVPHPELSLAESLWTSKPPPLFHEGAPYPPPLFIRDTYNQSIPQPPPRKIKRPKRK
  MYREEPTSIMNAIKLRPRQVLCDKCKNSVVAEKKEIRKGSSATDSSKYEDKKRRNESVTT
  VNKKLKTDHKVDGKNQNESQKRNAVVKVSNIAHSRGRVVKVSAQANTSKAQLSTKKVLQS
  KNMDHAKAREVLKIAKEKAQKKQNETSTSKNAHSKVHFTRRYQNPSSGSLPPRVRLKPQR
  YRNEENDSSLKTGLEKMRSGKMAPKPQSRCTSTRSAGEAPSENQSPSKGPEEASSEVQDT
  NEVHVPGDQDEPQTLGKKGSKNNISVYMTLNQKKSDSSSASVCSIDSTDDLKSSNSECSS
  SESFDFPPGSMHAPSTSSTSSSSKEEKKLSNSLKMKVFSKNVSKCVTPDGRTICVGDIVW
  AKIYGFPWWPARILTITVSRKDNGLLVRQEARISWFGSPTTSFLALSQLSPFLENFQSRF
  NKKRKGLYRKAITEAAKAAKQLTPEVRALLTQFET
• Function: Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes. Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z. Plays a role in facilitating transcriptional elongation and repression of spurious transcription initiation through regulation of histone acetylation. Essential for proper mitosis progression.

Molecular Interaction Atlas (MIA) of This DOT

7 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 PWWP domain-containing protein 2A (PWWP2A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PWWP domain-containing protein 2A (PWWP2A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PWWP domain-containing protein 2A (PWWP2A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PWWP domain-containing protein 2A (PWWP2A).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of PWWP domain-containing protein 2A (PWWP2A).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of PWWP domain-containing protein 2A (PWWP2A).	[9]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of PWWP domain-containing protein 2A (PWWP2A).	[10]

3 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 PWWP domain-containing protein 2A (PWWP2A).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of PWWP domain-containing protein 2A (PWWP2A).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PWWP domain-containing protein 2A (PWWP2A).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] 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.
• [6] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [7] 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.
• [8] 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.
• [9] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [10] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.