Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX46DKQ)

• DOT Name: Regulatory factor X-associated protein (RFXAP)
• Synonyms: RFX-associated protein; RFX DNA-binding complex 36 kDa subunit
• Gene Name: RFXAP
• Related Disease:
  MHC class II deficiency
  Neoplasm
  Severe combined immunodeficiency
• UniProt ID: RFXAP_HUMAN
• PDB ID: 2KW3
• Pfam ID: PF15289
• Sequence:
  MEAQGVAEGAGPGAASGVPHPAALAPAAAPTLAPASVAAAASQFTLLVMQPCAGQDEAAA
  PGGSVGAGKPVRYLCEGAGDGEEEAGEDEADLLDTSDPPGGGESAASLEDLEDEETHSGG
  EGSSGGARRRGSGGGSMSKTCTYEGCSETTSQVAKQRKPWMCKKHRNKMYKDKYKKKKSD
  QALNCGGTASTGSAGNVKLEESADNILSIVKQRTGSFGDRPARPTLLEQVLNQKRLSLLR
  SPEVVQFLQKQQQLLNQQVLEQRQQQFPGTSM
• Function: Part of the RFX complex that binds to the X-box of MHC II promoters.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Antigen processing and presentation (hsa04612)
  Tuberculosis (hsa05152)
  Primary immunodeficiency (hsa05340)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
MHC class II deficiency	DISWMI0G	Definitive	Autosomal recessive	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Altered Expression	[3]

19 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 Regulatory factor X-associated protein (RFXAP).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Regulatory factor X-associated protein (RFXAP).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Regulatory factor X-associated protein (RFXAP).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Regulatory factor X-associated protein (RFXAP).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Regulatory factor X-associated protein (RFXAP).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Regulatory factor X-associated protein (RFXAP).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Regulatory factor X-associated protein (RFXAP).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Regulatory factor X-associated protein (RFXAP).	[11]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Regulatory factor X-associated protein (RFXAP).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Regulatory factor X-associated protein (RFXAP).	[13]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Regulatory factor X-associated protein (RFXAP).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Regulatory factor X-associated protein (RFXAP).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Regulatory factor X-associated protein (RFXAP).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Regulatory factor X-associated protein (RFXAP).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Regulatory factor X-associated protein (RFXAP).	[18]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Regulatory factor X-associated protein (RFXAP).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Regulatory factor X-associated protein (RFXAP).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Regulatory factor X-associated protein (RFXAP).	[21]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Regulatory factor X-associated protein (RFXAP).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Regulatory factor X-associated protein (RFXAP).	[19]

References

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• [2] Association of high CD4-positive T cell infiltration with mutations in HLA class II-regulatory genes in microsatellite-unstable colorectal cancer.Cancer Immunol Immunother. 2015 Mar;64(3):357-66. doi: 10.1007/s00262-014-1638-4. Epub 2014 Dec 2.
• [3] Conserved residues of the bare lymphocyte syndrome transcription factor RFXAP determine coordinate MHC class II expression.Mol Immunol. 2006 Feb;43(5):395-409. doi: 10.1016/j.molimm.2005.03.008. Epub 2005 Apr 12.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [12] Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line. J Biol Chem. 2003 May 2;278(18):15633-40.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
• [15] 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.
• [16] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] 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.
• [19] 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.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [21] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [22] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.