PROSITE documentation PDOC51186
Gcn5-related N-acetyltransferase (GNAT) domain profiles


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 [3]. 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
  • 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
  • Escherichia coli rimI and rimJ, which acetylate the N-terminal alanine of ribosomal proteins S18 and S5, respectively (EC
  • Mycobacterium tuberculosis aminoglycoside 2'-N-acetyltransferase (aac), which acetylates the 2' hydroxyl or amino group of a broad spectrum of aminoglycoside antibiotics.
  • Bacillus subtilis bltD and paiA, which acetylate spermine and spermidine.
  • Escherichia coli uncharacterized protein YjdJ [6].
  • Animal N-acetyltransferase domain-containing protein 1 (NATD1 or GTLF3B) [6].
  • Arabidopsis thaliana minimal acetyltransferase At1g77540 [6].
  • 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 [7].
  • Vertebrate-like N-acetyl-L-gluatamate synthase (NAGS, EC, 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 [8].
  • 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 [6] and the third for the ATAT-type subfamily [7]. The fourth profile is directed against the vertebrate-like NAGS-type GNAT domain [8]. All the profiles we developed cover the entire GNAT domain.

Last update:

August 2014 / Text revised; profile added.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

GNAT, PS51186; Gcn5-related N-acetyltransferase (GNAT) domain profile  (MATRIX)

GNAT_ATAT, PS51730; Alpha-tubulin Gcn5-related N-acetyltransferase (GNAT) domain profile  (MATRIX)

GNAT_NAGS, PS51731; Vertebrate-like NAGS Gcn5-related N-acetyltransferase (GNAT) domain profile  (MATRIX)

GNAT_YJDJ, PS51729; Yjdj-type Gcn5-related N-acetyltransferase (GNAT) domain profile  (MATRIX)


1AuthorsNeuwald A.F. Landsman D.
TitleGCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein.
SourceTrends Biochem. Sci. 22:154-155(1997).
PubMed ID9175471

2AuthorsDyda F. Klein D.C. Hickman A.B.
TitleGCN5-related N-acetyltransferases: a structural overview.
SourceAnnu. Rev. Biophys. Biomol. Struct. 29:81-103(2000).
PubMed ID10940244

3AuthorsBurk D.L. Ghuman N. Wybenga-Groot L.E. Berghuis A.M.
TitleX-ray structure of the AAC(6')-Ii antibiotic resistance enzyme at 1.8 A resolution; examination of oligomeric arrangements in GNAT superfamily members.
SourceProtein Sci. 12:426-437(2003).
PubMed ID12592013

4AuthorsHe H. Ding Y. Bartlam M. Sun F. Le Y. Qin X. Tang H. Zhang R. Joachimiak A. Liu J. Zhao N. Rao Z.
TitleCrystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.
SourceJ. Mol. Biol. 325:1019-1030(2003).
PubMed ID12527305

5AuthorsVetting M.W. S de Carvalho L.P. Yu M. Hegde S.S. Magnet S. Roderick S.L. Blanchard J.S.
TitleStructure and functions of the GNAT superfamily of acetyltransferases.
SourceArch. Biochem. Biophys. 433:212-226(2005).
PubMed ID15581578

6AuthorsCort J.R. Ramelot T.A. Murray D. Acton T.B. Ma L.-C. Xiao R. Montelione G.T. Kennedy M.A.
TitleStructure of an acetyl-CoA binding protein from Staphylococcus aureus representing a novel subfamily of GCN5-related N-acetyltransferase-like proteins.
SourceJ. Struct. Funct. Genomics 9:7-20(2008).
PubMed ID18709443

7AuthorsKormendi V. Szyk A. Piszczek G. Roll-Mecak A.
TitleCrystal structures of tubulin acetyltransferase reveal a conserved catalytic core and the plasticity of the essential N terminus.
SourceJ. Biol. Chem. 287:41569-41575(2012).
PubMed ID23105108

8AuthorsZhao G. Jin Z. Allewell N.M. Tuchman M. Shi D.
TitleCrystal structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms.
SourcePLoS ONE 8:E70369-E70369(2013).
PubMed ID23894642

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