NACHT is an acronym standing for NAIP (neuronal apoptosis inhibitor protein), C2TA (MHC class 2 transcription activator), HET-E (incompatibility locus protein from Podospora anserina) and TP1 (telomerase-associated protein). The NACHT domain is an evolutionary conserved protein domain.
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. The NACHT domain has been named after NAIP, CIITA, HET-E and TP1. It is found in association with other domains, such as the CARD domain (IPR001315), the pyrin domain (IPR004020), the HEAT repeat domain (IPR004155), the WD40 repeat (IPR001680), the leucine-rich repeat (LRR) or the BIR repeat (IPR001370).
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.
Human proteins containing this domain include:
- NLRC3, NLRC4, NLRC5
- NLRP1, NLRP2, NLRP3, NLRP4, NLRP5, NLRP6, NLRP7, NLRP8, NLRP9, NLRP10, NLRP11, NLRP12, NLRP13, NLRP14, NLRX1
- NOD1, NOD2
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