The NACHT domain is an evolutionarily conserved protein domain. This NTPase domain is found in apoptosis proteins as well as those involved in MHC transcription.^[1] Its name reflects some of the proteins that contain it: NAIP (NLP family apoptosis inhibitor protein), CIITA (that is, C2TA or MHC class II transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TEP1 (that is, TP1 or telomerase-associated protein).

The NACHT domain contains 300 to 400 amino acids. It is a predicted nucleoside-triphosphatase (NTPase) domain, which is found in animal, fungal and bacterial proteins. It is found in association with other domains, such as the CARD domain (InterPro: IPR001315), the pyrin domain (InterPro: IPR004020), the HEAT repeat domain (InterPro: IPR004155), the WD40 repeat (InterPro: IPR001680), the leucine-rich repeat (LRR) or the BIR repeat (InterPro: IPR001370).^[1]

The NACHT domain consists of seven distinct conserved motifs, including the ATP/GTPase specific P-loop, the Mg²⁺-binding site (Walker A and B motifs, respectively) and five more specific motifs. The unique features of the NACHT domain include the prevalence of 'tiny' residues (glycine, alanine or serine) directly C-terminal of the Mg²⁺-coordinating aspartate in the Walker B motif, in place of a second acidic residue prevalent in other NTPases. A second acidic residue is typically found in the NACHT-containing proteins two positions downstream. Furthermore, the distal motif VII contains a conserved pattern of polar, aromatic and hydrophobic residues that is not seen in any other NTPase family.^[1]

Examples

Human proteins containing this domain include:

• CIITA
• NAIP
• NLRC3, NLRC4, NLRC5
• NLRP1, NLRP2, NLRP3, NLRP4, NLRP5, NLRP6, NLRP7, NLRP8, NLRP9, NLRP10, NLRP11, NLRP12, NLRP13, NLRP14, NLRX1
• NOD1, NOD2
• NWD1
• TEP1