Updated
May 2024
|
NAT2 allele (haplotype)(a) |
Retired & discontinued |
Nucleotide change(s)(b) |
Amino acid change(s)(b) |
Organism |
Literature |
|
(RABIT) |
|
Reference |
Reference |
Rabbit |
|
|
(MOUSE)Nat2*1 |
Nat2*8 |
Reference |
Reference |
Mouse |
|
|
(MOUSE)Nat2*2 |
Nat2*9 |
c.296A>T |
p.Asn99Ile |
Mouse |
|
|
(MUSMC)Nat2*3 |
Nat2*22 |
c.537T>C c.747C>T c.834A>G |
p.Asp179= p.Asn249= p.Lys278= |
Mouse |
|
|
(MUSSP)Nat2*4 |
Nat2*23 |
c.78A>T c.117T>C c.244C>A c.480C>T c.537T>C c.690A>G c.807T>A |
p.Glu26Asp p.Asn39= p.Leu82Met p.Tyr160= p.Asp179= p.Gly230= p.Thr269= |
Mouse |
|
|
(MESAU)Nat2*1 |
|
Reference |
Reference |
Syrian hamster |
|
|
(MESAU)Nat2*2 |
|
c.36T>C c.633A>G c.727C>T |
p.Tyr12= p.Thr211= p.Arg243Ter |
Syrian hamster |
|
|
(MESAU)Nat2*3 |
|
c.36T>C c.325C>T c.633A>G c.727C>T |
p.Tyr12= p.Leu109= p.Thr211= p.Arg243Ter |
Syrian hamster |
|
|
(RAT)Nat2*1 |
|
Reference |
Reference |
Rat |
|
|
(RAT)Nat2*2 |
|
c.361G>A c.399G>A c.522G>A c.796G>A |
p.Val121Ile p.Glu133= p.Glu174= p.Val266Ile |
Rat |
|
|
(RAT)Nat2*3 |
|
c.361G>A c.399G>A c.672C>T c.796G>A |
p.Val121Ile p.Glu133= p.Ser224= p.Val266Ile |
Rat |
|
|
(MACMU)NAT2*1 |
|
Reference |
Reference |
Rhesus macaque |
|
|
(MACMU) |
|
c.624C>T c.691G>A |
p.Tyr208= p.Val231Ile |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.463C>G c.624C>T c.691G>A |
p.Gly124= p.Gln155Glu p.Tyr208= p.Val231Ile |
Rhesus macaque |
|
|
(MACMU) |
|
c.556C>A |
p.His186Asn |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.463C>G |
p.Gly124= p.Gln155Glu |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.463C>G c.579G>A |
p.Gly124= p.Gln155Glu p.Thr193= |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.463C>G c.621A>T |
p.Gly124= p.Gln155Glu p.Thr207= |
Rhesus macaque |
|
|
(MACMU) |
|
c.145G>A c.372C>G c.463C>G c.621A>T |
p.Glu49Lys p.Gly124= p.Gln155Glu p.Thr207= |
Rhesus macaque |
|
|
(MACMU) |
|
c.124A>G c.372C>G c.463C>G |
p.Met42Val p.Gly124= p.Gln155Glu |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.463C>G c.552G>A |
p.Gly124= p.Gln155Glu p.Thr184= |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.424G>T c.463C>G c.579G>A |
p.Gly124= p.Asp142Tyr p.Gln155Glu p.Thr193= |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.463C>G c.662C>A c.795A>G |
p.Gly124= p.Gln155Glu p.Ser221Ter p.Glu265= |
Rhesus macaque |
|
|
(MACMU) |
|
c.372C>G c.624C>T c.691G>A |
p.Gly124= p.Tyr208= p.Val231Ile |
Rhesus macaque |
(a)
The gene symbols are assigned according to the current guidelines
of the NAT Gene Nomenclature
Committee. Previous
(b)
The position of SNPs in each
ORF is determined relative to the A of the ATG translation initiation codon,
which is always considered as number 1. The first methionine of each NAT
protein is amino acid number 1, with polymorphic amino acid positions
determined accordingly. The reference allele of each NAT2 gene (usually
the wild type allele or the first allele identified in a specific organism) is
assigned symbol NAT2*1.
(c)
Studied western European
house mouse (Mus musculus)
laboratory strains: i) inbred C57Bl/6J [6,7], Balb/c
[8], C3H/HeJ [9], 129/Ola
[10], CBA [10] (all carry
the Nat2*1 wild-type allele and are fast acetylators), A/J [6,7] and A/HeJ [9] (both
carry the Nat2*2 allele and are slow acetylators), ii) outbred CD1 [11] (mixed population carrying both Nat2*1 and Nat2*2
alleles), PO [10] and TO [10]
(both carry the Nat2*1 wild-type allele and are fast acetylators). Also,
the wild-derived inbred strains Mus musculus castaneus (southestern
Asian house mouse carrying the slow Nat2*3 allele) and Mus spretus (western
wild mouse carrying the slow Nat2*4 allele) [10].
For new
submissions or enquiries, please contact Dr. Sotiria Boukouvala (sboukouv@mbg.duth.gr).
[1] Hein,
D.W.; Boukouvala, S.; Grant, D.M.; Minchin, R.F. and Sim, E. (2008) Changes
in consensus arylamine N-acetyltransferase
gene nomenclature. Pharmacogenet. Genomics 18(4),
367-368.
[2] Sasaki,
Y.; Ohsako, S. and Deguchi, T. (1991) Molecular and genetic analyses of
arylamine N-acetyltransferase polymorphism of rabbit liver. J. Biol.
Chem. 266(20), 13243-13250.
[3] Blum, M.; Grant, D.M.; Demierre, A. and Meyer, U.A. (1989) Nucleotide sequence of a full-length cDNA for arylamine N-acetyltransferase from rabbit liver. Nucleic Acids Res. 17(9), 3589.
[4] Blum,
M.; Grant, D.M.; Demierre, A. and Meyer, U.A. (1989) N-acetylation
pharmacogenetics: A gene deletion causes absence of arylamine
N-acetyltransferase in liver of slow acetylator rabbits. Proc. Natl. Acad.
Sci.
[5] Blum,
M.; Heim, M. and Meyer, U.A. (1990) Nucleotide sequence of rabbit
[6] Martell,
K.J.; Vatsis, K.P. and Weber, W.W. (1991) Molecular genetic basis of rapid
and slow acetylation in mice. Mol. Pharmacol. 40(2), 218-227.
[7] Martell,
K.J.; Levy, G.N. and Weber, W.W. (1992) Cloned mouse N-acetyltransferases:
Enzymatic properties of expressed Nat1 and Nat2 gene products. Mol.
Pharmacol. 42(2), 265-272.
[8] Kelly, S.L. and Sim, E. (1994) Arylamine N-acetyltransferase in Balb/c mice: identification of a novel mouse isoenzyme by cloning and expression in vitro. Biochem. J. 302(2), 347-353.
[9] Fretland,
A.J.; Doll, M.A.; Gray, K.; Feng, Y. and Hein, D.W. (1997) Cloning,
expression and recombinant expression of
[10] Boukouvala,
S.; Price, N. and Sim, E. (2002) Identification and functional
characterization of novel polymorphisms associated with the genes for arylamine
N-acetyltransferases in mice. Pharmacogenetics 12(5), 385-394.
[11] Estrada, L.; Kanelakis, K.C.; Levy, G.N. and Weber, W.W. (2000) Tissue- and gender-specific expression of N-acetyltransferase 2 (NAT2*) during development of the outbred mouse strain CD-1. Drug Metab. Dispos. 28(2), 139-146.
[12] Ferguson,
R.J.; Doll, M.A.; Baumstark, B.R. and Hein, D.W. (1994) Polymorphic
arylamine N-acetyltransferase encoding gene (NAT2) from homozygous rapid
and slow acetylator congenic Syrian hamsters. Gene 140(2),
247-249.
[13] Ferguson,
R.J.; Doll, M.A.; Rustan, T.D. and Hein, D.W. (1996) Cloning, expression
and functional characterisation of rapid and slow acetylator polymorphic N-acetyltransferase
encoding genes of the Syrian hamster. Pharmacogenetics
6(1), 55-66.
[14] Land,
S.J.; Jones, R.E. and King, C.M. (1994) Biochemical and genetic analysis of
two acetyltransferases from hamster tissues that can metabolise aromatic amine
derivatives. Carcinogenesis 15(8), 1585-1595.
[15] Nagata,
K.; Ozawa, S.; Miyata, M.; Shimada, M.; Yamazoe, Y. and Kato, R. (1994)
Primary structure and molecular basis of polymorphic appearance of an
acetyltransferase (AT-II) in hamsters. Pharmacogenetics
4(2), 91-100.
[16] Doll,
M.A. and Hein, D.W. (1995) Cloning, sequencing and expression of NAT1 and
NAT2 encoding genes from rapid and slow acetylator inbred rats. Pharmacogenetics
5(4), 247-251.
[17] Walraven, J.M.; Doll, M.A. and Hein, D.W. (2006) Identification and characterization of functional rat arylamine N-acetyltransferase 3: comparisons with rat arylamine N-acetyltransferases 1 and 2. J. Pharmacol. Exp. Ther. 319(1), 369-375.
[18] Fakis,
G.; Boukouvala, S.; Kawamura, A. and Kennedy, S. (2007) Description of a
novel polymorphic gene encoding for arylamine N-acetyltransferase in the rhesus macaque (Macaca mulatta), a model animal for endometriosis. Pharmacogenet. Genomics 17(3), 181-188.
[19] Tsirka, T.;
Boukouvala, S.; Agianian, B.; Fakis, G. (2014) Polymorphism p.Val231Ile
alters substrate selectivity of drug-metabolizing arylamine N-acetyltransferase 2 (NAT2) isoenzyme
of rhesus macaque and human. Gene 536(1), 65-73.
[20] Boukouvala,
S.; Drakomathioulaki, N.; Papanikolaou, G.; Tsirka, T.; Veyssière, C.; Sabbagh,
A.; Crouau-Roy, B. and Fakis, G. (2021) Functional variability of rhesus
macaque (Macaca mulatta) NAT2 gene for drug-metabolising
arylamine N-acetyltransferase 2. Biochem. Pharmacol. 188,
114545