Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOV6EM9)

• DOT Name: PWWP domain-containing DNA repair factor 3B (PWWP3B)
• Synonyms: PWWP3B; Mutated melanoma-associated antigen 1-like protein 1; MUM1-like protein 1; PWWP domain-containing protein MUM1L1
• Gene Name: PWWP3B
• UniProt ID: PWP3B_HUMAN
• Pfam ID: PF20884 ; PF20886 ; PF20887
• Sequence:
  MESEYVLCNWKDQLWPAKVLSRSETSSNSKRKKAFSLEVQILSLDEKIKLDSTETKILNK
  SQIEAIAASLGLQSEDSAPPTEETAYGRSLKVALGILNERTNLSQASTSDEEEITMLSQN
  VPQKQSDSPPHKKYRKDEGDLPGCLEERENSACLLASSESDDSLYDDKSQAPTMVDTIPS
  EVETKSLQNSSWCETFPSLSEDNDEKENKNKIDISAVMSVHSAVKEESACVKDEKFAPPL
  SPLSSDMLIMPKALKEESEDTCLETLAVPSECSAFSENIEDPGEGPSNPCLDTSQNQPSM
  ESEMGAAACPGSCSRECEVSFSASNPVWDYSHLMSSERNFQRLDFEELEEEGQASDKSLL
  PSRINLSLLDDDEEDEELPRFILHYETHPFETGMIVWFKYQKYPFWPAVIKSIRRKERKA
  SVLFVEANMNSEKKGIRVNFRRLKKFDCKEKQMLVDKAREDYSESIDWCISLICDYRVRI
  GCGSFTGSLLEYYAADISYPVRKETKQDTFRNKFPKLHNEDAREPMAVTSQTKKMSFQKI
  LPDRMKAARDRANKNLVDFIVNAKGTENHLLAIVNGTKGSRWLKSFLNANRFTPCIETYF
  EDEDQLDEVVKYLQEVCNQIDQIMPTWIKDDKIKFILEVLLPEAIICSISAVDGLDYEAA
  EAKYLKGPCLGYRERELFDAKIIYEKRRKAPTNEAH

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 PWWP domain-containing DNA repair factor 3B (PWWP3B).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[9]

9 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 PWWP domain-containing DNA repair factor 3B (PWWP3B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of PWWP domain-containing DNA repair factor 3B (PWWP3B).	[11]

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] 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] 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.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] 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.
• [11] 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.