Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDI1MIV)

• DOT Name: Fanconi anemia core complex-associated protein 20 (FAAP20)
• Synonyms: FANCA-associated protein of 20 kDa; Fanconi anemia-associated protein of 20 kDa
• Gene Name: FAAP20
• Related Disease:
  Pancytopenia
  Fanconi anemia complementation group A
  Fanconi's anemia
• UniProt ID: FAP20_HUMAN
• PDB ID: 2MUQ; 2MUR; 3WWQ
• Pfam ID: PF15751 ; PF15750
• Sequence:
  MEAARRPRLGLSRRRPRPAGGPSGGRPWFLLGGDERERLWAELLRTVSPELILDHEVPSL
  PAFPGQEPRCGPEPTEVFTVGPKTFSWTPFPPDLWGPGRSYRLLHGAGGHLESPARSLPQ
  RPAPDPCRAPRVEQQPSVEGAAALRSCPMCQKEFAPRLTQLDVDSHLAQCLAESTEDVTW
• Function: Component of the Fanconi anemia (FA) complex required to recruit the FA complex to DNA interstrand cross-links (ICLs) and promote ICLs repair. Following DNA damage recognizes and binds 'Lys-63'-linked ubiquitin generated by RNF8 at ICLs and recruits other components of the FA complex. Promotes translesion synthesis via interaction with REV1.
• Reactome Pathway:
  PKR-mediated signaling (R-HSA-9833482)
  Fanconi Anemia Pathway (R-HSA-6783310)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pancytopenia	DISVKEHV	Strong	Biomarker	[1]
Fanconi anemia complementation group A	DIS8PZLI	Limited	Biomarker	[2]
Fanconi's anemia	DISGW6Q8	Limited	Biomarker	[2]

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 Fanconi anemia core complex-associated protein 20 (FAAP20).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Fanconi anemia core complex-associated protein 20 (FAAP20).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fanconi anemia core complex-associated protein 20 (FAAP20).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Fanconi anemia core complex-associated protein 20 (FAAP20).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Fanconi anemia core complex-associated protein 20 (FAAP20).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fanconi anemia core complex-associated protein 20 (FAAP20).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Fanconi anemia core complex-associated protein 20 (FAAP20).	[9]

References

• [1] Loss of Faap20 Causes Hematopoietic Stem and Progenitor Cell Depletion in Mice Under Genotoxic Stress.Stem Cells. 2015 Jul;33(7):2320-30. doi: 10.1002/stem.2048. Epub 2015 May 25.
• [2] Prolyl isomerization of FAAP20 catalyzed by PIN1 regulates the Fanconi anemia pathway.PLoS Genet. 2019 Feb 21;15(2):e1007983. doi: 10.1371/journal.pgen.1007983. eCollection 2019 Feb.
• [3] 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.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [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] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.