Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLH23GP)

• DOT Name: Adaptin ear-binding coat-associated protein 2 (NECAP2)
• Synonyms: NECAP endocytosis-associated protein 2; NECAP-2
• Gene Name: NECAP2
• Related Disease:
  Dermatomyositis
  Polymyositis
• UniProt ID: NECP2_HUMAN
• Pfam ID: PF07933
• Sequence:
  MEESGYESVLCVKPDVHVYRIPPRATNRGYRAAEWQLDQPSWSGRLRITAKGQMAYIKLE
  DRTSGELFAQAPVDQFPGTAVESVTDSSRYFVIRIEDGNGRRAFIGIGFGDRGDAFDFNV
  ALQDHFKWVKQQCEFAKQAQNPDQGPKLDLGFKEGQTIKLNIANMKKKEGAAGNPRVRPA
  STGGLSLLPPPPGGKTSTLIPPPGEQLAVGGSLVQPAVAPSSGGAPVPWPQPNPATADIW
  GDFTKSTGSTSSQTQPGTGWVQF
• Function: Involved in endocytosis.
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dermatomyositis	DIS50C5O	Strong	Biomarker	[1]
Polymyositis	DIS5DHFP	Strong	Biomarker	[1]

3 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 Adaptin ear-binding coat-associated protein 2 (NECAP2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Adaptin ear-binding coat-associated protein 2 (NECAP2).	[13]

References

• [1] Integrated comparison of the miRNAome and mRNAome in muscles of dermatomyositis and polymyositis reveals common and specific miRNA-mRNAs.Epigenomics. 2019 Jan;11(1):23-33. doi: 10.2217/epi-2018-0064. Epub 2018 Dec 7.
• [2] 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.
• [3] 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.
• [4] 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.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [8] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.