Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS3QVF1)

• DOT Name: N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25)
• Synonyms: Mitochondrial distribution and morphology protein 20; N-terminal acetyltransferase B complex subunit MDM20; NatB complex subunit MDM20; N-terminal acetyltransferase B complex subunit NAA25; p120
• Gene Name: NAA25
• Related Disease:
  Adult glioblastoma
  Colon cancer
  Colon carcinoma
  Glioblastoma multiforme
  Stroke
  Adenocarcinoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Capillary malformation-arteriovenous malformation syndrome
  Carcinoma of esophagus
  Ductal carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Head and neck neoplasm
  Head-neck squamous cell carcinoma
  Hypophosphatemia
  Hypothyroidism
  Invasive ductal breast carcinoma
  Isolated cleft lip
  Juvenile idiopathic arthritis
  Lung cancer
  Lung carcinoma
  Mucinous adenocarcinoma
  Multiple sclerosis
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Oral cancer
  Oral cavity carcinoma
  Pancreatic cancer
  Prostate disease
  Psoriasis
  Rheumatoid arthritis
  Squamous cell carcinoma
  Systemic lupus erythematosus
  Thiel-Behnke corneal dystrophy
  Type-1 diabetes
  Coronary heart disease
  Glioma
  Tetralogy of fallot
• UniProt ID: NAA25_HUMAN
• PDB ID: 6VP9; 7STX; 8G0L
• Pfam ID: PF09797
• Sequence:
  MATRGHVQDPNDRRLRPIYDYLDNGNNKMAIQQADKLLKKHKDLHCAKVLKAIGLQRTGK
  QEEAFTLAQEVAALEPTDDNSLQALTILYREMHRPELVTKLYEAAVKKVPNSEEYHSHLF
  MAYARVGEYKKMQQAGMALYKIVPKNPYYFWSVMSLIMQSISAQDENLSKTMFLPLAERM
  VEKMVKEDKIEAEAEVELYYMILERLGKYQEALDVIRGKLGEKLTSEIQSRENKCMAMYK
  KLSRWPECNALSRRLLLKNSDDWQFYLTYFDSVFRLIEEAWSPPAEGEHSLEGEVHYSAE
  KAVKFIEDRITEESKSSRHLRGPHLAKLELIRRLRSQGCNDEYKLGDPEELMFQYFKKFG
  DKPCCFTDLKVFVDLLPATQCTKFINQLLGVVPLSTPTEDKLALPADIRALQQHLCVVQL
  TRLLGLYHTMDKNQKLSVVRELMLRYQHGLEFGKTCLKTELQFSDYYCLLAVHALIDVWR
  ETGDETTVWQALTLLEEGLTHSPSNAQFKLLLVRIYCMLGAFEPVVDLYSSLDAKHIQHD
  TIGYLLTRYAESLGQYAAASQSCNFALRFFHSNQKDTSEYIIQAYKYGAFEKIPEFIAFR
  NRLNNSLHFAQVRTERMLLDLLLEANISTSLAESIKSMNLRPEEDDIPWEDLRDNRDLNV
  FFSWDPKDRDVSEEHKKLSLEEETLWLRIRSLTLRLISGLPSLNHPVEPKNSEKTAENGV
  SSRIDILRLLLQQLEATLETGKRFIEKDIQYPFLGPVPTRMGGFFNSGCSQCQISSFYLV
  NDIYELDTSGLEDTMEIQERIENSFKSLLDQLKDVFSKCKGDLLEVKDGNLKTHPTLLEN
  LVFFVETISVILWVSSYCESVLRPYKLNLQKKKKKKKETSIIMPPVFTSFQDYVTGLQTL
  ISNVVDHIKGLETHLIALKLEELILEDTSLSPEERKFSKTVQGKVQSSYLHSLLEMGELL
  KKRLETTKKLKI
• Function: Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. May play a role in normal cell-cycle progression.
• BioCyc Pathway: MetaCyc:ENSG00000111300-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Colon cancer	DISVC52G	Definitive	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Definitive	Altered Expression	[2]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Stroke	DISX6UHX	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[5]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[6]
Capillary malformation-arteriovenous malformation syndrome	DISMN03Q	Strong	Genetic Variation	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[8]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[9]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[8]
Head and neck neoplasm	DIS1OB2G	Strong	Genetic Variation	[10]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[11]
Hypophosphatemia	DIS9DZYF	Strong	Altered Expression	[12]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[13]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[14]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[15]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[4]
Mucinous adenocarcinoma	DISKNFE8	Strong	Biomarker	[16]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Genetic Variation	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Oral cancer	DISLD42D	Strong	Biomarker	[20]
Oral cavity carcinoma	DISZXMVL	Strong	Biomarker	[20]
Pancreatic cancer	DISJC981	Strong	Biomarker	[21]
Prostate disease	DISFVG19	Strong	Altered Expression	[22]
Psoriasis	DIS59VMN	Strong	Altered Expression	[23]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[6]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[4]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[6]
Thiel-Behnke corneal dystrophy	DIS3GK26	Strong	Biomarker	[24]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[25]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[26]
Glioma	DIS5RPEH	Limited	Biomarker	[27]
Tetralogy of fallot	DISMHFNW	Limited	Genetic Variation	[28]

9 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 N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[29]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[30]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[31]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[32]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[33]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[34]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[35]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[36]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of N-alpha-acetyltransferase 25, NatB auxiliary subunit (NAA25).	[37]

References

• [1] Interleukin-8 Secreted by Glioblastoma Cells Induces Microvascular Hyperpermeability Through NO Signaling Involving S-Nitrosylation of VE-Cadherin and p120 in Endothelial Cells.Front Physiol. 2019 Aug 8;10:988. doi: 10.3389/fphys.2019.00988. eCollection 2019.
• [2] miR-223 promotes colon cancer by directly targeting p120 catenin.Oncotarget. 2017 Jul 25;8(38):63764-63779. doi: 10.18632/oncotarget.19541. eCollection 2017 Sep 8.
• [3] p120 inhibits LPS/TNF-induced endothelial Ang2 synthesis and release in an NF-B independent fashion.Cytokine. 2019 Nov;123:154786. doi: 10.1016/j.cyto.2019.154786. Epub 2019 Jul 26.
• [4] Expression of nucleolar protein p120 in human lung cancer: difference in histological types as a marker for proliferation.Clin Cancer Res. 1997 Oct;3(10):1873-7.
• [5] Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease.Gene. 2001 Jun 27;271(2):159-69. doi: 10.1016/s0378-1119(01)00521-2.
• [6] Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis.Arthritis Rheum. 2009 Jul;60(7):2124-30. doi: 10.1002/art.24618.
• [7] RASA1 regulates the function of lymphatic vessel valves in mice.J Clin Invest. 2017 Jun 30;127(7):2569-2585. doi: 10.1172/JCI89607. Epub 2017 May 22.
• [8] Correlations of ALDH2 rs671 and C12orf30 rs4767364 polymorphisms with increased risk and prognosis of esophageal squamous cell carcinoma in the Kazak and Han populations in Xinjiang province.J Clin Lab Anal. 2018 Feb;32(2):e22248. doi: 10.1002/jcla.22248. Epub 2017 May 2.
• [9] Further evidence that E-cadherin is not a tumour suppressor gene in invasive ductal carcinoma of the breast: an immunohistochemical study.Histopathology. 2013 Apr;62(5):695-701. doi: 10.1111/his.12066. Epub 2013 Jan 24.
• [10] A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.PLoS Genet. 2011 Mar;7(3):e1001333. doi: 10.1371/journal.pgen.1001333. Epub 2011 Mar 17.
• [11] Gene-environment interactions of novel variants associated with head and neck cancer.Head Neck. 2012 Aug;34(8):1111-8. doi: 10.1002/hed.21867. Epub 2011 Nov 2.
• [12] Phosphatonin washout in Hyp mice proximal tubules: evidence for posttranscriptional regulation.Am J Physiol Renal Physiol. 2005 Feb;288(2):F363-70. doi: 10.1152/ajprenal.00217.2004. Epub 2004 Sep 28.
• [13] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [14] Correlation between E-cadherin and p120 expression in invasive ductal breast cancer with a lobular component and MRI findings.Virchows Arch. 2017 Dec;471(6):707-712. doi: 10.1007/s00428-017-2203-2. Epub 2017 Aug 4.
• [15] Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity.Nat Commun. 2017 Feb 24;8:14364. doi: 10.1038/ncomms14364.
• [16] Invasive lobular carcinoma with extracellular mucin production and HER-2 overexpression: a case report and further case studies.Diagn Pathol. 2010 Jun 15;5:36. doi: 10.1186/1746-1596-5-36.
• [17] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
• [18] p120-catenin in cancer - mechanisms, models and opportunities for intervention.J Cell Sci. 2013 Aug 15;126(Pt 16):3515-25. doi: 10.1242/jcs.134411.
• [19] Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.J Exp Clin Cancer Res. 2019 Mar 11;38(1):122. doi: 10.1186/s13046-019-1124-0.
• [20] Nucleolar protein p120 expression in oral carcinoma.Anticancer Res. 1999 Mar-Apr;19(2B):1423-6.
• [21] Up-regulation, nuclear import, and tumor growth stimulation of the adhesion protein p120 in pancreatic cancer.Gastroenterology. 2003 Apr;124(4):949-60. doi: 10.1053/gast.2003.50142.
• [22] A novel splice variant of the nuclear coactivator p120 functions strongly for androgen receptor: characteristic expression in prostate disease.Endocr J. 2008 Aug;55(4):657-65. doi: 10.1507/endocrj.k07e-133. Epub 2008 Jun 18.
• [23] Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ.J Invest Dermatol. 1991 Jul;97(1):73-9. doi: 10.1111/1523-1747.ep12478128.
• [24] Development of a Novel Vaccine Containing Binary Toxin for the Prevention of Clostridium difficile Disease with Enhanced Efficacy against NAP1 Strains.PLoS One. 2017 Jan 26;12(1):e0170640. doi: 10.1371/journal.pone.0170640. eCollection 2017.
• [25] Allelic variants in the PHTF1-PTPN22, C12orf30 and CD226 regions as candidate susceptibility factors for the type 1 diabetes in the Estonian population.BMC Med Genet. 2010 Jan 20;11:11. doi: 10.1186/1471-2350-11-11.
• [26] Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.Nat Genet. 2018 Sep;50(9):1335-1341. doi: 10.1038/s41588-018-0184-y. Epub 2018 Aug 13.
• [27] Expression of p120 nucleolar proliferating antigen in human gliomas and growth suppression of glioma cells by p120 ribozyme vector.Int J Oncol. 1999 Mar;14(3):417-24. doi: 10.3892/ijo.14.3.417.
• [28] Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.Hum Mol Genet. 2013 Apr 1;22(7):1473-81. doi: 10.1093/hmg/dds552. Epub 2013 Jan 7.
• [29] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [30] 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.
• [31] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [32] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [33] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [34] 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.
• [35] 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.
• [36] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [37] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.