Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLP1KR3)

• DOT Name: Nascent polypeptide-associated complex subunit alpha (NACA)
• Synonyms: NAC-alpha; Alpha-NAC; allergen Hom s 2
• Gene Name: NACA
• Related Disease:
  Alzheimer disease
  Chronic myelomonocytic leukaemia
  Neoplasm
  Rhabdomyosarcoma
  Atrial fibrillation
  Familial atrial fibrillation
• UniProt ID: NACA_HUMAN
• PDB ID: 3LKX; 3MCB; 3MCE; 7QWQ; 7QWR; 7QWS; 8P2K
• Pfam ID: PF19026 ; PF01849
• Sequence:
  MPGEATETVPATEQELPQPQAETGSGTESDSDESVPELEEQDSTQATTQQAQLAAAAEID
  EEPVSKAKQSRSEKKARKAMSKLGLRQVTGVTRVTIRKSKNILFVITKPDVYKSPASDTY
  IVFGEAKIEDLSQQAQLAAAEKFKVQGEAVSNIQENTQTPTVQEESEEEEVDETGVEVKD
  IELVMSQANVSRAKAVRALKNNSNDIVNAIMELTM
• Function: Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]
Rhabdomyosarcoma	DISNR7MS	moderate	Altered Expression	[3]
Atrial fibrillation	DIS15W6U	Limited	Biomarker	[4]
Familial atrial fibrillation	DISL4AGF	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Artesunate	DMR27C8	Approved	Nascent polypeptide-associated complex subunit alpha (NACA) decreases the response to substance of Artesunate.	[21]

16 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 Nascent polypeptide-associated complex subunit alpha (NACA).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[19]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Nascent polypeptide-associated complex subunit alpha (NACA).	[20]

References

• [1] Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome.J Investig Med. 2002 Jul;50(4):293-301. doi: 10.2310/6650.2002.33287.
• [2] Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and "virtual Northern" hybridization.Cancer Genet Cytogenet. 2003 Apr 15;142(2):149-52. doi: 10.1016/s0165-4608(02)00841-5.
• [3] Overexpression of the skNAC gene in human rhabdomyosarcoma cells enhances their differentiation potential and inhibits tumor cell growth and spreading.Clin Exp Metastasis. 2014 Dec;31(8):869-79. doi: 10.1007/s10585-014-9676-z. Epub 2014 Sep 11.
• [4] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [8] 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.
• [9] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] 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.
• [15] Proteomic signatures in thapsigargin-treated hepatoma cells. Chem Res Toxicol. 2011 Aug 15;24(8):1215-22. doi: 10.1021/tx200109y. Epub 2011 Jul 1.
• [16] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [17] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [20] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [21] Factors determining sensitivity or resistance of tumor cell lines towards artesunate. Chem Biol Interact. 2010 Apr 15;185(1):42-52.