NAT2 Alleles in Non-human Eukaryotes

*NAT2* allele (haplotype)^(a)	*Retired & discontinued NAT* allele^(a)**	Nucleotide change(s)^(b)	Amino acid change(s)^(b)	Organism	Literature
(RABIT)NAT21*	NAT22* NAT23*(deletion)	Reference	Reference	Rabbit (Oryctolagus cuniculus)	2-5
(MOUSE)Nat21*	Nat28*	Reference	Reference	Mouse (Mus musculus)	6-11^(c)
(MOUSE)Nat22*	Nat29*	296A>T	N99I	Mouse (Mus musculus)	6,7,9,11^(c)
(MUSMC)Nat23*	Nat222*	537T>C 747C>T 834A>G	Synonymous Synonymous Synonymous	Mouse (Mus musculus castaneus)	10^(c)
(MUSSP)Nat24*	Nat223*	78A>T 117T>C 244C>A 480C>T 537T>C 690A>G 807T>A	E26D Synonymous L82M Synonymous Synonymous Synonymous Synonymous	Mouse (Mus spretus)	10^(c)
(MESAU)Nat21*	NAT215*	Reference	Reference	Syrian hamster (Mesocricetus auratus)	12-15
(MESAU)Nat22*	NAT216A*	36T>C 633A>G 727C>T	Synonymous Synonymous R243Stop	Syrian hamster (Mesocricetus auratus)	12,13
(MESAU)Nat23*	NAT216B*	36T>C 325C>T 633A>G 727C>T	Synonymous Synonymous Synonymous R243Stop	Syrian hamster (Mesocricetus auratus)	15
(RAT)Nat21*	NAT220*	Reference	Reference	Rat (Rattus norvegicus)	16,17
(RAT)Nat22*	NAT221A*	361G>A 399G>A 522G>A 796G>A	V121I Synonymous Synonymous V266I	Rat (Rattus norvegicus)	16
(RAT)Nat23*	NAT221B*	361G>A 399G>A 672C>T 796G>A	V121I Synonymous Synonymous V266I	Rat (Rattus norvegicus)	16
(MACMU)NAT21*		Reference	Reference	Rhesus monkey (Macaca mulatta)	18
(MACMU)NAT22*		624C>T 691G>A	Synonymous V231I	Rhesus monkey (Macaca mulatta)	18

Footnotes

(a) The gene symbols are assigned according to the official guidelines of the NAT Gene Nomenclature Committee. Previous NAT alleles that did not follow the current convention have been retired and discontinued [1]. The alleles of rodents are written as Nat (first letter uppercase and second and third letter lowercase). The alleles of all other species are all uppercase (e.g. NAT).

(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 domesticus) 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).

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Literature

[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. USA 86(23), 9554-9557.

[5] Blum, M.; Heim, M. and Meyer, U.A. (1990) Nucleotide sequence of rabbit NAT2 encoding polymorphic liver arylamine N-acetyltransferase (NAT). Nucleic Acids Res. 18(17), 5295.

[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 NAT1, NAT2, and NAT3 derived from C3H/HeJ (rapid) and A/HeJ (slow) acetylator inbred mouse: Functional characterization of the activation and deactivation of aromatic amine carcinogens. Toxicol. Appl. Pharmacol. 142(2), 360-366.

[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.

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