Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8MJ9CJ)

• DOT Name: Peroxisomal membrane protein 11A (PEX11A)
• Synonyms: HsPEX11p; 28 kDa peroxisomal integral membrane protein; PMP28; Peroxin-11A; Peroxisomal biogenesis factor 11A; Protein PEX11 homolog alpha; PEX11-alpha
• Gene Name: PEX11A
• Related Disease:
  Obesity
  Zellweger spectrum disorders
  Peroxisome biogenesis disorder
• UniProt ID: PX11A_HUMAN
• Pfam ID: PF05648
• Sequence:
  MDAFTRFTNQTQGRDRLFRATQYTCMLLRYLLEPKAGKEKVVMKLKKLESSVSTGRKWFR
  LGNVVHAIQATEQSIHATDLVPRLCLTLANLNRVIYFICDTILWVRSVGLTSGINKEKWR
  TRAAHHYYYSLLLSLVRDLYEISLQMKRVTCDRAKKEKSASQDPLWFSVAEEETEWLQSF
  LLLLFRSLKQHPPLLLDTVKNLCDILNPLDQLGIYKSNPGIIGLGGLVSSIAGMITVAYP
  QMKLKTR
• Function: May be involved in peroxisomal proliferation and may regulate peroxisomes division. May mediate binding of coatomer proteins to the peroxisomal membrane. Promotes membrane protrusion and elongation on the peroxisomal surface.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway: PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	Strong	Biomarker	[1]
Zellweger spectrum disorders	DISW52CE	Limited	Biomarker	[2]
Peroxisome biogenesis disorder	DISBQ6QJ	No Known	Autosomal recessive	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Peroxisomal membrane protein 11A (PEX11A) affects the response to substance of Methotrexate.	[16]

12 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 Peroxisomal membrane protein 11A (PEX11A).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Peroxisomal membrane protein 11A (PEX11A).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Peroxisomal membrane protein 11A (PEX11A).	[11]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Peroxisomal membrane protein 11A (PEX11A).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peroxisomal membrane protein 11A (PEX11A).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peroxisomal membrane protein 11A (PEX11A).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Peroxisomal membrane protein 11A (PEX11A).	[14]

References

• [1] Pex11a deficiency causes dyslipidaemia and obesity in mice.J Cell Mol Med. 2019 Mar;23(3):2020-2031. doi: 10.1111/jcmm.14108. Epub 2018 Dec 25.
• [2] Peroxisomes in cardiomyocytes and the peroxisome / peroxisome proliferator-activated receptor-loop.Thromb Haemost. 2015 Mar;113(3):452-63. doi: 10.1160/TH14-06-0497. Epub 2015 Jan 22.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [11] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [15] 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.
• [16] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.