Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEZV4AP)

• DME Name: RNA cytidine acetyltransferase (hALP)
• Synonyms: N-acetyltransferase 10; N-acetyltransferase-like protein; 18S rRNA cytosine acetyltransferase; KIAA1709; NAT10
• Gene Name: NAT10
• UniProt ID: NAT10_HUMAN
• INTEDE ID: DME0007
• Gene ID: 55226
• EC Number:
  EC: 2.3.1.5
  Transferase
  Acyltransferase
  Acyltransferase
  EC: 2.3.1.5
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MHRKKVDNRIRILIENGVAERQRSLFVVVGDRGKDQVVILHHMLSKATVKARPSVLWCYK
  KELGFSSHRKKRMRQLQKKIKNGTLNIKQDDPFELFIAATNIRYCYYNETHKILGNTFGM
  CVLQDFEALTPNLLARTVETVEGGGLVVILLRTMNSLKQLYTVTMDVHSRYRTEAHQDVV
  GRFNERFILSLASCKKCLVIDDQLNILPISSHVATMEALPPQTPDESLGPSDLELRELKE
  SLQDTQPVGVLVDCCKTLDQAKAVLKFIEGISEKTLRSTVALTAARGRGKSAALGLAIAG
  AVAFGYSNIFVTSPSPDNLHTLFEFVFKGFDALQYQEHLDYEIIQSLNPEFNKAVIRVNV
  FREHRQTIQYIHPADAVKLGQAELVVIDEAAAIPLPLVKSLLGPYLVFMASTINGYEGTG
  RSLSLKLIQQLRQQSAQSQVSTTAENKTTTTARLASARTLYEVSLQESIRYAPGDAVEKW
  LNDLLCLDCLNITRIVSGCPLPEACELYYVNRDTLFCYHKASEVFLQRLMALYVASHYKN
  SPNDLQMLSDAPAHHLFCLLPPVPPTQNALPEVLAVIQVCLEGEISRQSILNSLSRGKKA
  SGDLIPWTVSEQFQDPDFGGLSGGRVVRIAVHPDYQGMGYGSRALQLLQMYYEGRFPCLE
  EKVLETPQEIHTVSSEAVSLLEEVITPRKDLPPLLLKLNERPAERLDYLGVSYGLTPRLL
  KFWKRAGFVPVYLRQTPNDLTGEHSCIMLKTLTDEDEADQGGWLAAFWKDFRRRFLALLS
  YQFSTFSPSLALNIIQNRNMGKPAQPALSREELEALFLPYDLKRLEMYSRNMVDYHLIMD
  MIPAISRIYFLNQLGDLALSAAQSALLLGIGLQHKSVDQLEKEIELPSGQLMGLFNRIIR
  KVVKLFNEVQEKAIEEQMVAAKDVVMEPTMKTLSDDLDEAAKEFQEKHKKEVGKLKSMDL
  SEYIIRGDDEEWNEVLNKAGPNASIISLKSDKKRKLEAKQEPKQSKKLKNRETKNKKDMK
  LKRKK
• Function: This enzyme catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs. It catalyzes ac4C modification of a broad range of mRNAs, enhancing mRNA stability and translation. In addition to RNA acetyltransferase activity, also able to acetylate lysine residues of proteins, such as histones, microtubules, p53/TP53 and MDM2, in vitro.
• Reactome Pathway: rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DME

14 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Allopurinol	DMLPAOB	Hyperuricaemia	5C55.Y	Approved	[1]
Arbekacin	DMHTXSL	Bacterial infection	1A00-1C4Z	Approved	[2]
Caffeine	DMKBJWP	Orthostatic hypotension	BA21	Approved	[3]
Clonazepam	DMTO13J	Epilepsy	8A60-8A68	Approved	[4]
Dihydralazine	DMZIXU9	Hypertension	BA00-BA04	Approved	[5]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[6]
Hydralazine	DMU8JGH	Hypertension	BA00-BA04	Approved	[7]
Mesalazine	DMOL5IU	Ulcerative colitis	DD71	Approved	[8]
Netilmicin	DMRD1QK	Bacterial infection	1A00-1C4Z	Approved	[9]
Procainamide	DMNMXR8	Ventricular arrhythmias	BC71	Approved	[10]
Sulfadiazine	DMTW3R8	Rheumatic fever	1B40-1B42	Approved	[11]
Sulfamethoxazole	DMB08GE	Bacterial infection	1A00-1C4Z	Approved	[12]
Sulfapyridine	DMIUYFH	Dermatitis herpetiformis	EB44	Approved	[13]
Tobramycin	DMUI0CH	Bacterial infection	1A00-1C4Z	Approved	[14]

2 Discontinued Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metamizole	DM79GRO	Fever	MG26	Withdrawn from market	[15]
Octopamine	DMLQVTJ	Thrombosis	DB61-GB90	Discontinued in Phase 2a	[16]

2 Investigative Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aminobenzoic acid	DMNGW2M	N. A.	N. A.	Investigative	[17]
Phenazone	DMCE985	Discovery agent	N.A.	Investigative	[18]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	3.44E-14	3.19E-01	7.91E-01
Alopecia	ED70	Skin from scalp	5.19E-01	1.01E-01	3.63E-01
Alzheimer's disease	8A20	Entorhinal cortex	8.46E-03	-4.02E-02	-2.28E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	9.39E-01	-4.37E-02	-4.88E-01
Aortic stenosis	BB70	Calcified aortic valve	9.07E-01	-1.44E-01	-1.67E-01
Apnea	7A40	Hyperplastic tonsil	1.57E-01	-1.30E-01	-2.62E-01
Arthropathy	FA00-FA5Z	Peripheral blood	1.34E-01	-1.92E-01	-1.19E+00
Asthma	CA23	Nasal and bronchial airway	6.58E-01	4.82E-02	1.20E-01
Atopic dermatitis	EA80	Skin	7.56E-04	1.12E-01	1.20E+00
Autism	6A02	Whole blood	2.21E-01	1.34E-01	5.05E-01
Autoimmune uveitis	9A96	Peripheral monocyte	1.83E-01	1.85E-01	1.04E+00
Autosomal dominant monocytopenia	4B04	Whole blood	7.21E-01	-4.89E-02	-4.56E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.51E-02	-7.73E-02	-3.71E-01
Batten disease	5C56.1	Whole blood	4.68E-01	-8.22E-02	-7.24E-01
Behcet's disease	4A62	Peripheral blood	1.38E-01	-1.52E-01	-6.46E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	5.01E-01	3.70E-02	2.95E-01
Bladder cancer	2C94	Bladder tissue	9.55E-01	-3.72E-02	-1.74E-01
Breast cancer	2C60-2C6Z	Breast tissue	1.36E-93	5.06E-01	1.73E+00
Cardioembolic stroke	8B11.20	Whole blood	3.29E-04	-3.74E-01	-1.44E+00
Cervical cancer	2C77	Cervical tissue	5.84E-03	-3.29E-01	-8.77E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	3.63E-01	-5.02E-02	-6.14E-02
Chronic hepatitis C	1E51.1	Whole blood	2.47E-01	3.85E-02	2.62E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	9.54E-01	3.88E-02	1.78E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	9.26E-01	4.16E-04	1.35E-03
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.30E-01	-1.28E-01	-7.19E-01
Colon cancer	2B90	Colon tissue	2.03E-95	9.61E-01	3.19E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.82E-01	1.00E-01	2.67E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	9.70E-01	5.39E-01	1.40E+00
Endometriosis	GA10	Endometrium tissue	7.76E-01	-8.49E-03	-3.69E-02
Familial hypercholesterolemia	5C80.00	Peripheral blood	2.09E-02	1.30E-01	8.45E-01
Familial hypercholesterolemia	5C80.00	Whole blood	5.28E-03	1.68E-01	5.67E-01
Gastric cancer	2B72	Gastric tissue	1.02E-03	6.92E-01	9.17E+00
Glioblastopma	2A00.00	Nervous tissue	2.61E-25	2.12E-01	6.47E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	6.23E-01	3.05E-01	5.15E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	2.06E-04	1.87E+00	2.35E+00
Head and neck cancer	2D42	Head and neck tissue	1.05E-05	1.50E-01	6.59E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	2.74E-01	1.90E-01	7.25E-01
Huntington's disease	8A01.10	Whole blood	2.62E-01	-5.54E-02	-3.62E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	6.13E-01	1.41E-01	5.05E-01
Immunodeficiency	4A00-4A20	Peripheral blood	4.42E-01	-2.31E-02	-3.01E-01
Influenza	1E30	Whole blood	2.00E-04	-1.14E+00	-6.90E+00
Interstitial cystitis	GC00.3	Bladder tissue	1.49E-03	-4.49E-01	-2.96E+00
Intracranial aneurysm	8B01.0	Intracranial artery	5.79E-01	-9.78E-03	-4.78E-02
Irritable bowel syndrome	DD91.0	Rectal colon tissue	4.26E-01	-2.09E-02	-4.13E-02
Ischemic stroke	8B11	Peripheral blood	3.20E-01	-1.75E-01	-6.19E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	2.30E-14	-4.73E-01	-1.28E+00
Lateral sclerosis	8B60.4	Skin	1.34E-01	2.36E-01	1.54E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	7.69E-01	-1.02E-02	-1.99E-02
Liver cancer	2C12.0	Liver tissue	2.13E-08	4.21E-01	1.05E+00
Liver failure	DB99.7-DB99.8	Liver tissue	7.84E-01	-8.30E-03	-3.17E-02
Lung cancer	2C25	Lung tissue	2.29E-47	5.02E-01	1.65E+00
Lupus erythematosus	4A40	Whole blood	8.41E-04	-2.59E-01	-3.92E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	6.63E-01	1.19E-02	9.35E-02
Major depressive disorder	6A70-6A7Z	Whole blood	3.27E-01	-7.24E-02	-1.43E-01
Melanoma	2C30	Skin	1.53E-03	2.30E-01	5.50E-01
Multiple myeloma	2A83.1	Peripheral blood	8.76E-01	-1.69E-01	-3.29E-01
Multiple myeloma	2A83.1	Bone marrow	4.55E-06	5.95E-01	3.58E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	1.35E-01	-1.66E-01	-5.82E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	8.68E-01	-1.58E-02	-5.16E-02
Myelofibrosis	2A20.2	Whole blood	8.89E-03	-5.23E-01	-3.23E+00
Myocardial infarction	BA41-BA50	Peripheral blood	7.31E-02	-1.64E-01	-2.33E-01
Myopathy	8C70.6	Muscle tissue	7.07E-01	2.79E-01	4.61E-01
Neonatal sepsis	KA60	Whole blood	7.09E-09	-3.39E-01	-7.26E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.06E-06	5.59E-01	2.70E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	2.53E-01	-9.15E-02	-3.15E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	5.24E-01	-1.57E-01	-3.66E-01
Olive pollen allergy	CA08.00	Peripheral blood	9.85E-01	1.18E-01	3.57E-01
Oral cancer	2B6E	Oral tissue	5.99E-02	3.49E-01	6.51E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	5.48E-01	2.99E-02	7.89E-02
Osteoporosis	FB83.1	Bone marrow	2.51E-01	-2.34E-01	-6.22E-01
Ovarian cancer	2C73	Ovarian tissue	4.55E-03	2.49E-01	1.43E+00
Pancreatic cancer	2C10	Pancreas	8.19E-02	-2.63E-01	-8.32E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	6.43E-01	-1.57E-01	-5.94E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	2.40E-02	-1.81E-01	-9.73E-01
Pituitary cancer	2D12	Pituitary tissue	1.98E-01	4.91E-02	1.31E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	1.05E-01	1.39E-01	3.92E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	5.47E-01	-2.06E-02	-1.83E-01
Polycythemia vera	2A20.4	Whole blood	1.09E-13	-4.66E-01	-2.38E+00
Pompe disease	5C51.3	Biceps muscle	1.17E-02	2.75E-01	8.25E-01
Preterm birth	KA21.4Z	Myometrium	4.68E-01	-1.85E-01	-4.93E-01
Prostate cancer	2C82	Prostate	1.40E-01	-1.58E-01	-5.57E-01
Psoriasis	EA90	Skin	1.53E-02	1.17E-01	4.09E-01
Rectal cancer	2B92	Rectal colon tissue	2.05E-06	8.87E-01	4.91E+00
Renal cancer	2C90-2C91	Kidney	2.06E-02	4.22E-01	9.87E-01
Retinoblastoma	2D02.2	Uvea	7.43E-09	1.36E+00	4.76E+00
Rheumatoid arthritis	FA20	Synovial tissue	7.52E-01	1.47E-02	4.56E-02
Rhinovirus infection	CA42.1	Nasal epithelium tissue	3.12E-01	5.26E-02	3.61E-01
Schizophrenia	6A20	Prefrontal cortex	6.00E-01	8.90E-02	2.34E-01
Schizophrenia	6A20	Superior temporal cortex	9.32E-01	3.08E-02	2.05E-01
Scleroderma	4A42.Z	Whole blood	2.42E-08	-5.49E-01	-3.98E+00
Seizure	8A60-8A6Z	Whole blood	5.53E-01	-7.99E-03	-1.57E-02
Sensitive skin	EK0Z	Skin	1.89E-01	6.36E-02	4.35E-01
Sepsis with septic shock	1G41	Whole blood	1.13E-33	-4.89E-01	-1.12E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.39E-02	-3.67E-01	-1.16E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	4.89E-03	-6.17E-01	-1.37E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	7.91E-01	7.83E-02	2.03E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	1.29E-01	3.17E-01	1.47E+00
Skin cancer	2C30-2C3Z	Skin	7.55E-01	1.26E-01	4.02E-01
Thrombocythemia	3B63	Whole blood	2.19E-04	-2.71E-01	-1.71E+00
Thrombocytopenia	3B64	Whole blood	7.56E-01	-6.14E-02	-1.31E-01
Thyroid cancer	2D10	Thyroid	4.92E-02	-7.75E-02	-3.12E-01
Tibial muscular dystrophy	8C75	Muscle tissue	9.67E-02	-1.60E-01	-6.92E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	2.49E-02	-3.13E-01	-2.01E+00
Type 2 diabetes	5A11	Liver tissue	9.17E-01	8.82E-02	3.14E-01
Ureter cancer	2C92	Urothelium	6.67E-01	1.27E-01	5.86E-01
Uterine cancer	2C78	Endometrium tissue	6.42E-01	3.71E-02	1.09E-01
Vitiligo	ED63.0	Skin	8.04E-02	1.85E-01	9.55E-01

References

• [1] Xanthine oxidase inhibition by allopurinol affects the reliability of urinary caffeine metabolic ratios as markers for N-acetyltransferase 2 and CYP1A2 activities. Eur J Clin Pharmacol. 1999 Jan;54(11):869-76.
• [2] The novel enzymatic 3''-N-acetylation of arbekacin by an aminoglycoside 3-N-acetyltransferase of Streptomyces origin and the resulting activity. J Antibiot (Tokyo). 1998 Aug;51(8):735-42.
• [3] A population and family study of N-acetyltransferase using caffeine urinary metabolites. Clin Pharmacol Ther. 1993 Aug;54(2):134-41.
• [4] Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam. Drug Metab Lett. 2007 Jan;1(1):3-5.
• [5] The influence of the acetylator phenotype for the clinical use of dihydralazine. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23 Suppl 1:S74-8.
• [6] Arylamine N-acetyltransferase in human red blood cells. Biochem Pharmacol. 1992 Sep 25;44(6):1099-104.
• [7] Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension. Clin Pharmacol Ther. 1981 May;29(5):588-93.
• [8] NAT1 genotypes do not predict response to mesalamine in patients with ulcerative colitis. Z Gastroenterol. 2008 Mar;46(3):259-65.
• [9] Aminoglycoside resistance resulting from tight drug binding to an altered aminoglycoside acetyltransferase. Antimicrob Agents Chemother. 2003 May;47(5):1577-83.
• [10] Effect of H2-receptor antagonists on rat liver cytosolic acetyl CoA:arylamine N-acetyltransferase activity. Drug Metab Dispos. 1992 Jan-Feb;20(1):74-8.
• [11] Identification of cytochrome P450 and arylamine N-acetyltransferase isoforms involved in sulfadiazine metabolism. Drug Metab Dispos. 2005 Jul;33(7):969-76.
• [12] Crystallization and preliminary X-ray characterization of arylamine N-acetyltransferase C (BanatC) from Bacillus anthracis. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Oct 1;63(Pt 10):862-4.
• [13] Effects of NAT2 polymorphism on SASP pharmacokinetics in Chinese population. Clin Chim Acta. 2009 Sep;407(1-2):30-5.
• [14] Genetic analysis of bacterial acetyltransferases: identification of amino acids determining the specificities of the aminoglycoside 6'-N-acetyltransferase Ib and IIa proteins. J Bacteriol. 1992 May;174(10):3196-203.
• [15] N-acetyltransferase 2 polymorphisms and susceptibility to infant leukemia with maternal exposure to dipyrone during pregnancy. Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3037-43.
• [16] [N-acetylation of biogenic amines in Drosophila virilis]. Genetika. 1997 Jun;33(6):788-92.
• [17] Leukemia inhibitory factor decreases the arylamine N-acetyltransferase activity in human cumulus granulosa cells. J Assist Reprod Genet. 2001 Dec;18(12):660-4.
• [18] Evaluation of the influence of diabetes mellitus on antipyrine metabolism and CYP1A2 and CYP2D6 activity. Pharmacotherapy. 2000 Feb;20(2):182-90.