Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWZVRX2)

• DOT Name: FLYWCH-type zinc finger-containing protein 1 (FLYWCH1)
• Gene Name: FLYWCH1
• Related Disease:
  Acute myelogenous leukaemia
  Colorectal carcinoma
  Coronary heart disease
• UniProt ID: FWCH1_HUMAN
• PDB ID: 2RPR
• Pfam ID: PF04500 ; PF15423 ; PF16662
• Sequence:
  MPLPEPSEQEGESVKAGQEPSPKPGTDVIPAAPRKPREFSKLVLLTASDQDEDGVGSKPQ
  EVHCVLSLEMAGPATLASTLQILPVEEQGGVVQPALEMPEQKCSKLDAAAPQSLEFLRTP
  FGGRLLVLESFLYKQEKAVGDKVYWKCRQHAELGCRGRAITRGLRATVMRGHCHAPDEQG
  LEARRQREKLPSLALPEGLGEPQGPEGPGGRVEEPLEGVGPWQCPEEPEPTPGLVLSKPA
  LEEEEAPRALSLLSLPPKKRSILGLGQARPLEFLRTCYGGSFLVHESFLYKREKAVGDKV
  YWTCRDHALHGCRSRAITQGQRVTVMRGHCHQPDMEGLEARRQQEKAVETLQAGQDGPGS
  QVDTLLRGVDSLLYRRGPGPLTLTRPRPRKRAKVEDQELPTQPEAPDEHQDMDADPGGPE
  FLKTPLGGSFLVYESFLYRREKAAGEKVYWTCRDQARMGCRSRAITQGRRVTVMRGHCHP
  PDLGGLEALRQREKRPNTAQRGSPGGPEFLKTPLGGSFLVYESFLYRREKAAGEKVYWTC
  RDQARMGCRSRAITQGRRVMVMRRHCHPPDLGGLEALRQREHFPNLAQWDSPDPLRPLEF
  LRTSLGGRFLVHESFLYRKEKAAGEKVYWMCRDQARLGCRSRAITQGHRIMVMRSHCHQP
  DLAGLEALRQRERLPTTAQQEDPEKIQVQLCFKTCSPESQQIYGDIKDVRLDGESQ
• Function: Transcription cofactor. Negatively regulates transcription activation by catenin beta-1 CTNNB1, perhaps acting by competing with TCF4 for CTNNB1 binding. May play a role in DNA-damage response signaling. Binds specifically to DNA sequences at peri-centromeric chromatin loci.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of FLYWCH-type zinc finger-containing protein 1 (FLYWCH1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of FLYWCH-type zinc finger-containing protein 1 (FLYWCH1).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of FLYWCH-type zinc finger-containing protein 1 (FLYWCH1).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of FLYWCH-type zinc finger-containing protein 1 (FLYWCH1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of FLYWCH-type zinc finger-containing protein 1 (FLYWCH1).	[5]

References

• [1] Increased FLYWCH1 Expression is Negatively Correlated with Wnt/-catenin Target Gene Expression in Acute Myeloid Leukemia Cells.Int J Mol Sci. 2019 Jun 4;20(11):2739. doi: 10.3390/ijms20112739.
• [2] FLYWCH1, a Novel Suppressor of Nuclear -Catenin, Regulates Migration and Morphology in Colorectal Cancer.Mol Cancer Res. 2018 Dec;16(12):1977-1990. doi: 10.1158/1541-7786.MCR-18-0262. Epub 2018 Aug 10.
• [3] Expression quantitative trait Loci acting across multiple tissues are enriched in inherited risk for coronary artery disease.Circ Cardiovasc Genet. 2015 Apr;8(2):305-15. doi: 10.1161/CIRCGENETICS.114.000640. Epub 2015 Jan 11.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] 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.
• [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.