The NACHT domain is an evolutionarily conserved
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
. This
NTPase domain is found in
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s as well as those involved in
MHC transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
.
Its name reflects some of the proteins that contain it:
NAIP (NLP family apoptosis
inhibitor protein
The inhibitor protein (IP) is situated in the mitochondrial matrix and protects the cell against rapid ATP hydrolysis during momentary ischaemia
Ischemia American and British English spelling differences#ae and oe, or ischaemia is a restric ...
),
CIITA
CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and c ...
(that is, C2TA or
MHC class II
MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial ce ...
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 acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s. It is a predicted
nucleoside-triphosphatase (NTPase) domain, which is found in
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
,
fungal
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
and
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
l proteins. It is found in association with other domains, such as the
CARD domain
Caspase recruitment domains, or caspase activation and recruitment domains (CARDs), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate th ...
(), the
pyrin domain
A pyrin domain (PYD, also known as PAAD/DAPIN) is a protein domain and a subclass of protein motif known as the death fold, the 4th and most recently discovered member of the death domain superfamily (DDF). It was originally discovered in the pyr ...
(), the
HEAT repeat domain
A HEAT repeat is a protein tandem repeat structural motif composed of two alpha helices linked by a short loop. HEAT repeats can form alpha solenoids, a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" i ...
(), the
WD40 repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold togethe ...
(), the
leucine-rich repeat
A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats common ...
(LRR) or the
BIR repeat ().
The NACHT domain consists of seven distinct conserved motifs, including the ATP/GTPase specific P-loop, the Mg
2+-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 Mg
2+-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.
Examples
Human proteins containing this domain include:
*
CIITA
CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and c ...
*
NAIP
*
NLRC3
NLRC3, short for NOD-like receptor family CARD domain containing 3, is an intracellular protein that plays a role in the immune system. It was previously known as ''nucleotide-binding oligomerization domain, leucine rich repeat and CARD domain c ...
,
NLRC4
NLR family CARD domain-containing protein 4 is a protein that in humans is encoded by the ''NLRC4'' gene.
Structure
The NLRC4 protein is highly conserved across mammalian species. It bears homology to the ''C. elegans'' Ced4 protein. It contai ...
,
NLRC5
NLRC5, short for NOD-like receptor family CARD domain containing 5, is an intracellular protein that plays a role in the immune system. NLRC5 is a pattern recognition receptor implicated in innate immunity to viruses potentially by regulating in ...
*
NLRP1
NLRP1 encodes NACHT, LRR, FIIND, CARD domain and PYD domains-containing protein 1 in humans. NLRP1 was the first protein shown to form an inflammasome. Material was copied from this source, which is available under Creative Commons Attribution 4. ...
,
NLRP2
NACHT, LRR and PYD domains-containing protein 2 is a protein that in humans is encoded by the ''NLRP2'' gene.
NALP proteins, such as NALP2, are characterized by an N-terminal pyrin domain (PYD) and are involved in the activation of caspase-1 (CA ...
,
NLRP3
NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1.
NLRP3 is ...
,
NLRP4
NACHT, LRR and PYD domains-containing protein 4 is a protein that in humans is encoded by the ''NLRP4'' gene.
NALPs are cytoplasmic proteins that form a subfamily within the larger CATERPILLER protein family. Most short NALPs, such as NALP4, have ...
,
NLRP5
NLRP5, short for NOD-like receptor family pyrin domain containing 5, is an intracellular protein that plays a role in early embryogenesis. NLRP5 is also known as NACHT, LRR and PYD domains-containing protein 5 (NALP5), Mater protein homolog (MAT ...
,
NLRP6
NLRP6, short for NOD-like receptor family pyrin domain containing 6, is an intracellular protein that plays a role in the immune system. It is also known as NALP6, PYPAF5, PAN3, and CLR11.4, and is one of 14 pyrin domain containing members of the ...
,
NLRP7,
NLRP8,
NLRP9,
NLRP10
NLRP10, short for NOD-like receptor family pyrin domain containing 10, is an intracellular protein of mammals that functions in apoptosis and the immune system. It is also known as NALP10, NOD8, PAN5, Pynod, and CLR11.1, and is one of 14 pyrin d ...
,
NLRP11,
NLRP12
NACHT, LRR and PYD domains-containing protein 12 is a protein that in humans is encoded by the ''NLRP12'' gene.
NALPs are cytoplasmic proteins that form a subfamily within the larger CATERPILLER protein family. Most short NALPs, such as NALP12, ...
,
NLRP13,
NLRP14,
NLRX1
NLRX1 or NLR family member X1, short for ''nucleotide-binding oligomerization domain, leucine rich repeat containing X1'' is a protein that in humans is encoded by the ''NLRX1'' gene. It is also known as ''NOD-like receptor X1'', ''NLR family, X1' ...
*
NOD1
Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor that in humans is encoded by the ''NOD1'' gene. It recognizes bacterial molecules and stimulates an immune reaction .
NOD1 protein contains a caspase recr ...
,
NOD2
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the ''NOD2'' g ...
*
NWD1
NWD1, short for NACHT and WD repeat domain containing 1, is a gene found in vertebrates, which encodes a protein that contains a NACHT domain and a WD40 repeat domain. It was originally identified during a search for immune system genes in zebrafi ...
*
TEP1
References
Protein domains
{{InterPro content, IPR007111