The N-acetyltransferases (NAT) (EC 2.3.1.-) are enzymes that use acetyl
coenzyme A (CoA) to transfer an acetyl group to a substrate, a reaction
implicated in various functions from bacterial antibiotic resistance to
mammalian circadian rhythm and chromatin remodeling. The Gcn5-related
N-acetyltransferases (GNAT) catalyze the transfer of the acetyl from the CoA
donor to a primary amine of the acceptor. The GNAT proteins share a domain
composed of four conserved sequence motifs A-D [1,2]. This GNAT domain is
named after yeast GCN5 (from General Control Nonrepressed) and related histone
acetyltransferases (HATs) like Hat1 and PCAF. HATs acetylate lysine residues
of amino terminal histone tails, resulting in transcription activation.
Another category of GNAT, the aminoglycoside N-acetyltransferases, confer
antibiotic resistance by catalyzing the acetylation of amino groups in
aminoglycoside antibiotics . GNAT proteins can also have anabolic and
catabolic functions in both prokaryotes and eukaryotes [1,2,3,4,5].
The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to
7 β strands (B) and 4 helices (H) in the topology
B1-H1-H2-B2-B3-B4-H3-B5-H4-B6, followed by a C-terminal strand which may be
from the same monomer or contributed by another [2,5] (see <PDB:1YGH>). Motifs
D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core
[2,4,5], while the N-terminal motif C (B1-H1) is less conserved.
Some proteins known to contain a GNAT domain:
- Yeast GCN5 and Hat1, which are histone acetyltransferases (EC 220.127.116.11).
- Human PCAF, a histone acetyltransferase.
- Mammalian serotonin N-acetyltransferase (SNAT) or arylalkylamine NAT
(AANAT), which acetylates serotonin into a circadian neurohormone that may
participate in light-dark rhythms, and human mood and behavior.
- Mammalian glucosamine 6-phosphate N-acetyltransferase (GNA1) (EC 18.104.22.168).
- Escherichia coli rimI and rimJ, which acetylate the N-terminal alanine of
ribosomal proteins S18 and S5, respectively (EC 22.214.171.124).
- Mycobacterium tuberculosis aminoglycoside 2'-N-acetyltransferase (aac),
which acetylates the 2' hydroxyl or amino group of a broad spectrum of
- Bacillus subtilis bltD and paiA, which acetylate spermine and spermidine.
- Escherichia coli uncharacterized protein YjdJ .
- Animal N-acetyltransferase domain-containing protein 1 (NATD1 or GTLF3B)
- Arabidopsis thaliana minimal acetyltransferase At1g77540 .
- Animal α-tubulin N-acetyltransferases (TATs), acetylate Lys-40 of
α-tubulin in most eukaryotes. TATs show preference for tubulin already
incorporated in microtubules, and acetylation is associated predominantly
with stable microtubules such as those found in cilia and axons. TATs show
high sequence conservation from flagellates to humans .
- Vertebrate-like N-acetyl-L-gluatamate synthase (NAGS, EC 126.96.36.199), catalyze
the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate
(NAG). They include not only vertebrate NAGS, but also fungal NAGS and
NAGK, and bacterial bifunctional NAGS/K .
- Bacteria-like NAGS, includes most bacterial and plant NAGS.
As the GNAT domain has largely diverged we developed several profiles. The
first one is general and detects several subfamilies of GNAT domains. The
second is specific for the YjtD-type subfamily  and the third for the ATAT-type subfamily . The fourth profile is directed against the vertebrate-like
NAGS-type GNAT domain . All the profiles we developed cover the entire GNAT
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to