Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWMA7LK)

• DOT Name: N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16)
• Synonyms: NMDA receptor-regulated 1-like protein; NARG1-like protein
• Gene Name: NAA16
• Related Disease:
  Adenoma
  Breast cancer
  Breast carcinoma
  Endometriosis
  Lupus
  Prostate cancer
  Prostate carcinoma
  Systemic sclerosis
  Type-1/2 diabetes
• UniProt ID: NAA16_HUMAN
• Pfam ID: PF12569 ; PF07719
• Sequence:
  MPNVLLPPKESNLFKRILKCYEQKQYKNGLKFCKMILSNPKFAEHGETLAMKGLTLNCLG
  KKEEAYEFVRKGLRNDVKSHVCWHVYGLLQRSDKKYDEAIKCYRNALKLDKDNLQILRDL
  SLLQIQMRDLEGYRETRYQLLQLRPTQRASWIGYAIAYHLLKDYDMALKLLEEFRQTQQV
  PPNKIDYEYSELILYQNQVMREADLLQESLEHIEMYEKQICDKLLVEEIKGEILLKLGRL
  KEASEVFKNLIDRNAENWCYYEGLEKALQISTLEERLQIYEEISKQHPKAITPRRLPLTL
  VPGERFRELMDKFLRVNFSKGCPPLFTTLKSLYYNTEKVSIIQELVTNYEASLKTCDFFS
  PYENGEKEPPTTLLWVQYFLAQHFDKLGQYSLALDYINAAIASTPTLIELFYMKAKIYKH
  IGNLKEAAKWMDEAQSLDTADRFINSKCAKYMLRANMIKEAEEMCSKFTREGTSAMENLN
  EMQCMWFQTECISAYQRLGRYGDALKKCHEVERHFFEITDDQFDFHTYCMRKMTLRAYVD
  LLRLEDILRRHAFYFKAARSAIEIYLKLYDNPLTNESKQQEINSENLSAKELKKMLSKQR
  RAQKKAKLEEERKHAERERQQKNQKKKRDEEEEEASGLKEELIPEKLERVENPLEEAVKF
  LIPLKNLVADNIDTHLLAFEIYFRKGKFLLMLQSVKRAFAINSNNPWLHECLIRFSKSVS
  NHSNLPDIVSKVLSQEMQKIFVKKDLESFNEDFLKRNATSLQHLLSGAKMMYFLDKSRQE
  KAIAIATRLDETIKDKDVKTLIKVSEALLDGSFGNCSSQYEEYRMACHNLLPFTSAFLPA
  VNEVDNPNVALNHTANYDVLANEI
• Function: Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Endometriosis	DISX1AG8	Strong	Altered Expression	[3]
Lupus	DISOKJWA	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[5]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[5]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[14]

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 decreases the methylation of N-alpha-acetyltransferase 16, NatA auxiliary subunit (NAA16).	[12]

References

• [1] Lack of association between the polyadenylation polymorphism in the NAT1 (acetyltransferase 1) gene and colorectal adenomas.Carcinogenesis. 1996 Oct;17(10):2125-9. doi: 10.1093/carcin/17.10.2125.
• [2] Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer.Mol Med. 2009 May-Jun;15(5-6):160-5. doi: 10.2119/molmed.2008.00136. Epub 2009 Mar 6.
• [3] Association between endometriosis and N-acetyl transferase 2 polymorphisms in a UK population.Mol Hum Reprod. 2001 Nov;7(11):1079-83. doi: 10.1093/molehr/7.11.1079.
• [4] Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus.Adv Exp Med Biol. 1999;455:147-52. doi: 10.1007/978-1-4615-4857-7_21.
• [5] Acetylation genotype and the genetic susceptibility to prostate cancer in a southern European population.Prostate. 2005 Aug 1;64(3):246-52. doi: 10.1002/pros.20241.
• [6] N-acetyltransferase 2 polymorphism in patients with diabetes mellitus.Cell Biochem Funct. 2007 Jul-Aug;25(4):407-11. doi: 10.1002/cbf.1314.
• [7] 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.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [13] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.