GNAT domain (IPR000182)
Short name: GNAT_dom
Overlapping homologous superfamilies
- Acyl-CoA N-acyltransferase (IPR016181)
- GNAT domain (IPR000182)
- PanZ, acetyltransferase (GNAT) domain (IPR040448)
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 [PMID: 9175471, PMID: 10940244]. 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 [PMID: 12592013]. GNAT proteins can also have anabolic and catabolic functions in both prokaryotes and eukaryotes [PMID: 9175471, PMID: 10940244, PMID: 12592013, PMID: 12527305, PMID: 15581578].
The acetyltransferase/GNAT domain forms a structurally conserved fold of 6 to 7 beta 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 [PMID: 10940244, PMID: 15581578]. Motifs D (B2-B3), A (B4-H3) and B (B5-H4) are collectively called the HAT core [PMID: 10940244, PMID: 12527305, PMID: 15581578], 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 18.104.22.168).
- 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 22.214.171.124).
- Escherichia coli rimI and rimJ, which acetylate the N-terminal alanine of ribosomal proteins S18 and S5, respectively (EC 126.96.36.199).
- 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.
This entry represents the entire GNAT domain.