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NAT2


Official Full Name
N-acetyltransferase 2
Organism
Homo sapiens
Gene ID
10
Background
This gene encodes an enzyme that functions to both activate and deactivate arylamine and hydrazine drugs and carcinogens. Polymorphisms in this gene are responsible for the N-acetylation polymorphism in which human populations segregate into rapid, intermediate, and slow acetylator phenotypes. Polymorphisms in this gene are also associated with higher incidences of cancer and drug toxicity. A second polymorphic arylamine N-acetyltransferase gene (NAT1), is located near this gene (NAT2). [provided by RefSeq, Sep 2019]
Synonyms
AAC2; PNAT; NAT-2

Cat.No. Product Name Price
SHH216785 shRNA set against Human NAT2(NM_000015.2) Inquiry
SHH221712 shRNA set against Human SLC38A1(NM_001077484.1) Inquiry
SHH349496 shRNA set against Mouse NAT2 (NM_010874.3) Inquiry
SHH410928 shRNA set against Rat SLC38A1 (NM_138832.1) Inquiry
SHR187032 shRNA set against Human RNF38(NM_022781.4) Inquiry
SHR186996 shRNA set against Human RNF38(NM_194328.2) Inquiry
SHR186954 shRNA set against Rat Rnf38(NM_134467.1) Inquiry
SHR186916 shRNA set against Human RNF38(NM_194329.2) Inquiry
SHH410924 shRNA set against Mouse SLC38A1 (NM_134086.4) Inquiry
SHH397320 shRNA set against Rat RNF38 (NM_134467.1) Inquiry
SHR205644 shRNA set against Rat Slc38a1(NM_138832.1) Inquiry
SHH397316 shRNA set against Mouse RNF38 (NM_175201.5) Inquiry
SHH397312 shRNA set against Human RNF38 (NM_194332.2) Inquiry
SHH349500 shRNA set against Rat NAT2 (NM_053854.1) Inquiry
SHH349492 shRNA set against Human NAT2 (NM_000015.2) Inquiry
SHH216803 shRNA set against Rat Nat2(NM_053854.1) Inquiry
SHH410920 shRNA set against Human SLC38A1 (NM_030674.3) Inquiry
SHW003358 shRNA set against Chicken SLC38A1 (NM_001199603) Inquiry
Cat.No. Product Name Price
CDCR380617 Rat Nat2 ORF Clone(NM_053854.1) Inquiry
MiUTR1R-07003 RNF38 miRNA 3'UTR clone Inquiry
MiUTR1R-04121 NAT2 miRNA 3'UTR clone Inquiry
MiUTR1H-09553 SLC38A1 miRNA 3'UTR clone Inquiry
MiUTR1H-08904 RNF38 miRNA 3'UTR clone Inquiry
MiUTR1H-08903 RNF38 miRNA 3'UTR clone Inquiry
CDFR014260 Rat Slc38a1 cDNA Clone(NM_138832.1) Inquiry
CDFR013585 Rat Nat2 cDNA Clone(NM_053854.1) Inquiry
CDFR013501 Rat Rnf38 cDNA Clone(NM_134467.1) Inquiry
CDFH017907 Human SLC38A1 cDNA Clone(NM_001077484.1) Inquiry
CDFG012497 Human RNF38 cDNA Clone(NM_194332.2) Inquiry
CDFG003949 Human RNF38 cDNA Clone(NM_022781.4) Inquiry
MiUTR1R-07470 SLC38A1 miRNA 3'UTR clone Inquiry
MiUTR3H-12334 NAT2 miRNA 3'UTR clone Inquiry
CDCL185431 Human NAT2 ORF clone(NM_000015.2) Inquiry
CDCR325298 Human RNF38 ORF Clone(NM_194330.2) Inquiry
CDCB180292 Rabbit NAT2 ORF clone (NM_001082186.1) Inquiry
CDCB183317 Rabbit SLC38A1 ORF clone (XM_008259626.1) Inquiry
CDCB193671 Rabbit RNF38 ORF clone (XM_008266062.1) Inquiry
CDCH074650 human RNF38 ORF clone (NM_194329.2) Inquiry
CDCH074652 human RNF38 ORF clone (NM_022781.4) Inquiry
CDCH074656 Mouse Rnf38 ORF clone (NM_001038993.3) Inquiry
CDCH400977 Mouse SLC38A1 ORF clone(NM_001166458.1) Inquiry
CDCR241101 Mouse Slc38a1 ORF Clone(NM_001166456.1) Inquiry
CDCR241907 Mouse Nat2 ORF Clone(NM_001168577.1) Inquiry
CDCR249461 Mouse Nat2 ORF Clone(NM_010874.3) Inquiry
CDCS417756 Human RNF38 ORF Clone (BC033786) Inquiry
CDCS407226 Human SLC38A1 ORF Clone (BC010620) Inquiry
CDCS405354 Human NAT2 ORF Clone (BC015878) Inquiry
CDCR381307 Rat Slc38a1 ORF Clone(NM_138832.1) Inquiry
CDCR381253 Rat Rnf38 ORF Clone(NM_134467.1) Inquiry
CDCR265921 Mouse Slc38a1 ORF Clone(NM_134086.4) Inquiry
CDCR345188 Human SLC38A1 ORF Clone(NM_001077484.1) Inquiry
CDCR325300 Human RNF38 ORF Clone(NM_194332.2) Inquiry
CDCR272691 Mouse Rnf38 ORF Clone(NM_175201.5) Inquiry
CDCB164833 Chicken SLC38A1 ORF Clone (NM_001199603) Inquiry

Detailed Information

The N-acetyltransferase 2 gene (NAT2) is located in the short arm 2 region 2 (8p22) of human 8th pair of chromosomes. The coding region is 870 bp long and encodes the drug phase II metabolic enzyme N- Acetyltransferase. There are mainly 7 mutations in the NAT2 gene polymorphism, and some site mutations will directly lead to changes in the activity of the encoded metabolic enzymes, which may affect the inactivation or activation of some drug metabolism and carcinogens, thus leading to some drug-related diseases and cancers occur.

The Role of NAT2

NAT2 is widely found in many organelles in the human body. It has different degrees of expression in the liver, large intestine, small intestine, stomach, lung, prostate, larynx, bladder, esophagus, etc., and is dominant in liver and intestinal epithelial cells. The study found that the activity and the expression decreased in the order of duodenum, jejunum, ileum, colon and rectum, and there were differences between different populations and individuals. Differences in tissue-specific expression make the NAT2 genotype have different effects on different organs and tissue carcinogenesis. At present, the common allelic mutations occur mainly at seven sites, such as 191, 282, 341, 481, 590, 803, and 857. Among them, the mutations of Asians 481, 590, 857, and 191 are the most common. According to the acetylation ability, the NAT2 gene phenotype can be divided into fast acetylation type, intermediate type and slow acetylation type.

Aromatic amines and heterocyclic amines are found in tobacco, high-temperature cooked meats, pharmaceuticals, and certain chemical raw materials and products. They have been identified as one of the former carcinogens. The acetylation process in which NAT2 participates in the catalysis is an important part of the metabolism of this substance in the body. It is generally believed that aromatic amines (heterocyclic amines) enter the human body, first catalyzed by cytochrome P450 in the liver to form N-hydroxyaromatic amines (heterocyclic amines), and then form N-acetyl aromatic under the catalysis of NAT2. The latter contains highly reactive N ions, which are easily incorporated into DNA to form DNA adducts, causing DNA mutations and cell carcinogenesis. When the NAT2 gene is mutated, it may cause changes in enzyme activity or quantity, and may also cause an increase in enzyme instability, thereby increasing the N-acetoxy-based product and inducing canceration.

Dual functions of NAT2 in bladder carcinogenesis. Figure 1. Dual functions of NAT2 in bladder carcinogenesis. (Quan, L., et al. 2016)

The Relationship between NAT2 and Disease

The occurrence of a mutation in the NAT2 allele often results in decreased enzyme activity, decreased stability, and decreased expression. This impairs the ability of acetylation to metabolize, resulting in differences in individual susceptibility to disease. The distribution of NAT2 gene polymorphism is closely related to liver damage caused by anti-tuberculosis drugs. A study of 241 Indonesian tuberculosis patients (50 patients with liver injury and 191 patients without liver injury) found that slow-acetylation (NAT2* 6) and anti-tuberculosis drug-induced liver damage (anti- tuberculosis drug - induced Hepatic injury, ADIH) related. The risk of ADIH in NAT2 slow acetylation is 3.45 times higher than that of fast acetylation and intermediate acetylation. Studies have shown that the slow acetylation of NAT2 is a high risk factor for drug-induced liver injury in tuberculosis patients. NAT2 is the most well-recognized gene in the susceptibility gene for anti-tuberculosis drugs. It is the main metabolic enzyme of isoniazid and rifampicin, which affects the metabolism of isoniazid and rifampicin. During isoniazid metabolism, isoniazid is first acetylated by NAT2 to acetyl isoniazid and then hydrolyzed to produce monoacetylhydrazine.

References:

  1. Quan, L. , Chattopadhyay, K. , Nelson, H. H. , Chan, K. K. , & Yuan, J. M. . (2016). Differential association for n-acetyltransferase 2 genotype and phenotype with bladder cancer risk in chinese population. Oncotarget, 7(26).
  2. Nasr, R. , Temraz, S. , Mukherji, D. , Shamseddine, A. , & Zgheib, N. K. . (2017). Distribution and role of n-acetyltransferase 2 genetic polymorphisms in bladder cancer risk in a lebanese population. Asian Pacific Journal of Cancer Prevention Apjcp, 18(9), 2561-2568.
  3. Yuliwulandari, R. , Susilowati, R. W. , Razari, I. , Viyati, K. , Umniyati, H. , & Prayuni, K. . (0). N‐acetyltransferase 2 polymorphism and acetylation profiles in buginese ethnics of indonesia. Annals of Human Genetics.
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