Details of Drug Off-Target (DOT)

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

• DOT Name: F-box only protein 44 (FBXO44)
• Synonyms: F-box protein FBX30; F-box/G-domain protein 3
• Gene Name: FBXO44
• Related Disease:
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate neoplasm
• UniProt ID: FBX44_HUMAN
• PDB ID: 3WSO; 5B4N
• Pfam ID: PF12937 ; PF04300
• Sequence:
  MAVGNINELPENILLELFTHVPARQLLLNCRLVCSLWRDLIDLVTLWKRKCLREGFITED
  WDQPVADWKIFYFLRSLHRNLLHNPCAEEGFEFWSLDVNGGDEWKVEDLSRDQRKEFPND
  QVKKYFVTSYYTCLKSQVVDLKAEGYWEELMDTTRPDIEVKDWFAARPDCGSKYQLCVQL
  LSSAHAPLGTFQPDPATIQQKSDAKWREVSHTFSNYPPGVRYIWFQHGGVDTHYWAGWYG
  PRVTNSSITIGPPLP
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
• Tissue Specificity: Abundantly expressed in brain and kidney. Expressed at lower levels in heart, spleen and liver.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]

2 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 F-box only protein 44 (FBXO44).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of F-box only protein 44 (FBXO44).	[9]

6 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 F-box only protein 44 (FBXO44).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of F-box only protein 44 (FBXO44).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of F-box only protein 44 (FBXO44).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of F-box only protein 44 (FBXO44).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of F-box only protein 44 (FBXO44).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of F-box only protein 44 (FBXO44).	[10]

References

• [1] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [2] Global analysis of differentially expressed genes in androgen-independent prostate cancer.Prostate Cancer Prostatic Dis. 2007;10(2):167-74. doi: 10.1038/sj.pcan.4500933. Epub 2007 Jan 2.
• [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] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.