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Literature summary extracted from

  • Sim, E.; Westwood, I.; Fullam, E.
    Arylamine N-acetyltransferases (2007), Expert. Opin. Drug Metab. Toxicol., 3, 169-184.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.3.1.5 medicine C1095A SNP outside the NAT1 coding region is associated with increased homocysteine. The C1095A SNP is found most frequently in the NAT1 allele 1*10 and is shown to have increase NAT1 activity or to have no effect. C1095A SNP appears at increased frequency in bladder cancer and Alzheimer's disease Homo sapiens
2.3.1.5 medicine epidemiological studies of birth defects indicate that NAT1 polymorphisms are associated with problems of neural tube closure in spina bifida and with cleft lip and palate. Limp formation defects are also associated with NAT1 polymorphism Homo sapiens
2.3.1.5 medicine mutant alleles resulting in a decrease in NAT1 activity are found to be protective against spina bifida Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.5 E26D/L82M in Mus spretus mice, slow acetylation is associated with an unstable Nat2 protein in which there are two amino acid changes Glu26Asp and Leu82Met Mus spretus
2.3.1.5 additional information effect of deleting NAT gene: slows growth, increases sensitivity to isoniazid, changes colony morphology, reduces the thickness of the cell wall of individual cells, decreases mycolic acid and complex lipids but not phosholipids, leads to intracellular killing of Mycobacterium bovis in macrophages Mycobacterium tuberculosis variant bovis
2.3.1.5 additional information Nat1 knockout mice do not show an obvious phenotype, apart from the expected reduction in arylamine metabolism Mus musculus
2.3.1.5 additional information Nat2 knockout mice do not show an obvious phenotype, apart from the expected reduction in arylamine metabolism. From analyses following breeding studies it appears that lack of NAT2 affects the sex ratios in offspring such that there is an excess of females among heterozygotes Mus musculus
2.3.1.5 additional information Nat3 knockout mice: lack of Nat3 has no effect in the metabolism of arylamines by mice Mus musculus
2.3.1.5 additional information overexpression of human NAT1 in mice results in serious developmental problems: deevelopmentally deleterious effects are observed in which embryos either do not survive or show malformations with a phenotype in which the tail is kinked, reminiscent of a spina-bifida phenotype Homo sapiens
2.3.1.5 R64W change from arginine to tryptophane at residue 64 seriously affects protein stability. Mutant is shown to cluster in cytosolic aggresomes and is rapidly ubiquitinylated and degraded Mesocricetus auratus
2.3.1.5 R64W SNP resulting in an inactive protein Homo sapiens
2.3.1.5 R99I Mus musculus A/J slow acetylating strain harbours a R99I mutation in the Nat2 gene, causing instability and degradation of the mutant protein Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.5 hydrogen peroxide inhibition is caused by oxidation at the active site cysteine Homo sapiens
2.3.1.5 peroxynitrite inhibition is caused by oxidation at the active site cysteine Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.1.5 cytosol
-
 Mesocricetus auratus 5829
-

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.5 Canis lupus familiaris
-
 no activity in Canis lupus familiaris
-
2.3.1.5 Homo sapiens
-
-
-
2.3.1.5 Mesocricetus auratus
-
-
-
2.3.1.5 Mus musculus
-
-
-
2.3.1.5 Mus spretus
-
-
-
2.3.1.5 Mycobacterium tuberculosis variant bovis
-
 NAT gene is essential for survival of Mycobacterium bovis
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.5 blastocyst
-
 Homo sapiens
-
2.3.1.5 cerebellar Purkinje cell
-
 Homo sapiens
-
2.3.1.5 erythrocyte
-
 Homo sapiens
-
2.3.1.5 lymphocyte
-
 Homo sapiens
-
2.3.1.5 additional information NAT1 and NAT2 expression differ during development Homo sapiens
-
2.3.1.5 neural tube
-
 Homo sapiens
-
2.3.1.5 placenta expressed in placenta during the first trimester of embryonic development Homo sapiens
-
2.3.1.5 spleen transcript only detected in spleen Mus musculus
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2.3.1.5 additional information
-
 low enzymatic activity as a recombinant protein Mus musculus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.5 acetyl-CoA + p-aminobenzoic acid
-
 Mus musculus CoA + N-acetyl-p-aminobenzoic acid
-
 ?
2.3.1.5 acetyl-CoA + p-aminobenzoylglutamate
-
 Mus musculus CoA + N-[(4-acetylamino)]benzoyl-L-glutamate
-
 ?
2.3.1.5 acetyl-CoA + p-aminobenzoylglutamate
-
 Homo sapiens CoA + N-[(4-acetylamino)]benzoyl-L-glutamate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.5 arylamine N-acetyltransferase
-
 Mycobacterium tuberculosis variant bovis
2.3.1.5 arylamine N-acetyltransferase 1
-
 Mus musculus
2.3.1.5 arylamine N-acetyltransferase 1
-
 Homo sapiens
2.3.1.5 arylamine N-acetyltransferase 1
-
 Mesocricetus auratus
2.3.1.5 arylamine N-acetyltransferase 1
-
 Mus spretus
2.3.1.5 NAT
-
 Mycobacterium tuberculosis variant bovis
2.3.1.5 NAT1
-
 Mus musculus
2.3.1.5 NAT1
-
 Homo sapiens
2.3.1.5 NAT1
-
 Mesocricetus auratus
2.3.1.5 NAT2
-
 Mus musculus
2.3.1.5 NAT2
-
 Mus spretus
2.3.1.5 NAT2 equivalent of human NAT1 in terms of tissue distribution, gene organization, C-terminal sequence analysis and substrate specificity Mus musculus
2.3.1.5 NAT2 equivalent of human NAT1 in terms of tissue distribution, gene organization, C-terminal sequence analysis and substrate specificity Mus spretus
2.3.1.5 NAT3 in mice there are three functional polymorphic NAT genes. NAT3 is highly polymorphic Mus musculus

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
2.3.1.5 40 47 NAT enzymes unfold cooperatively with concomitant loss of activity at 40-47°C Homo sapiens