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NOD-like Receptor
The nucleotide-binding oligomerization domain-like receptors, or NOD-like receptors (NLRs) (also known as nucleotide-binding leucine-rich repeat receptors), are intracellular sensors of pathogen-associated molecular patterns (PAMPs) that enter the cell via phagocytosis or pores, and damage-associated molecular patterns (DAMPs) that are associated with cell stress. They are types of pattern recognition receptors (PRRs), and play key roles in the regulation of innate immune response. NLRs can cooperate with toll-like receptors (TLRs) and regulate inflammatory and apoptotic response. They are found in lymphocytes, macrophages, dendritic cells and also in non-immune cells, for example in epithelium. NLRs are highly conserved through evolution. Their homologs have been discovered in many different animal species (APAF1) and also in the plant kingdom ( disease-resistance R protein). Structure NLRs contain 3 domains – central NACHT (NOD or NBD – nucleotide-binding domain) domai ...
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Pathogen-associated Molecular Pattern
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. A vast array of different types of molecules can serve as PAMPs, including glycans and glycoconjugates. PAMPs activate innate immune responses, protecting the host from infection, by identifying some conserved nonself molecules. Bacterial lipopolysaccharides (LPSs), endotoxins found on the cell membranes of gram-negative bacteria, are considered to be the prototypical class of PAMPs. LPSs are specifically recognised by TLR4, a recognition receptor of the innate immune system. Other PAMPs include bacterial flagellin (recognized by TLR5), lipoteichoic acid from gram-positive bacteria (recognized by TLR2), peptidoglycan (recognized by TLR2), and nucleic acid variants normally associated with viruses, such as double-stranded RNA (dsRNA), recognized by ...
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Inhibitor Of Apoptosis Domain
The inhibitor of apoptosis domain -- also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR -- is a structural motif found in proteins with roles in apoptosis, cytokine production, and chromosome segregation. Proteins containing BIR are known as inhibitor of apoptosis proteins (IAPs), or BIR-containing proteins (BIRPs or BIRCs), and include BIRC1 ( NAIP), BIRC2 (cIAP1), BIRC3 (cIAP2), BIRC4 (xIAP), BIRC5 ( survivin) and BIRC6. BIR domains belong to the zinc-finger domain family and characteristically have a number of invariant amino acid residues, including 3 conserved cysteines and one conserved histidine, which coordinate a zinc ion. They are typically composed of 4-5 alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ... and a three-strand ...
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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 (MATER), PYPAF8, PAN11, and CLR19.8, and is one of 14 pyrin domain containing members of the NOD-like receptor family of cytoplasmic receptors known to mammals. In humans, the NLRP5 protein is encoded by the ''NLRP5'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... References Further reading * * * * LRR proteins NOD-like receptors {{Transmembranereceptor-stub ...
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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 an N-terminal pyrin (MEFV; MIM 608107) domain (PYD), followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. The long NALP, NALP1 (MIM 606636), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase recruitment domain (CARD). NALPs are implicated in the activation of proinflammatory caspases (e.g., CASP1 Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis ...; MIM 147678) via their involvement in multiprotein complexes called inflammasomes (Tschopp et ...
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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 expressed predominantly in macrophages and as a component of the inflammasome, detects products of damaged cells such as extracellular ATP and crystalline uric acid. Activated NLRP3 in turn triggers an immune response. Mutations in the NLRP3 gene are associated with a number of organ specific autoimmune diseases. Nomenclature NACHT, LRR, and PYD are respectively acronyms for: * NACHT – NAIP (neuronal apoptosis inhibitor protein), C2TA heterokaryon_incompatibility)_and_TP1_(telomerase-associated_protein_1) *_ MHC,_HET-E_(Podospora_anserina#Heterokaryon_incompatibility">heterokaryon_incompatibility)_and_TP1_(telomerase-associated_protein_1) *_Leucine-rich_repeat">LRR_–_"leucine-rich_repeat"__and_is_synonymous_with_NLR,_for_''_or_' ...
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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 (CASP1; MIM 147678) by Toll-like receptors(see TLR4). They may also be involved in protein complexes that activate proinflammatory caspases (Tschopp et al., 2003). upplied by OMIMref name="entrez"> Function The NLRP2 gene is one of the family members of nucleotide-binding and leucine-rich repeat receptor (NLR). Information from many literature sources indicates that an N-terminal pyrin effector domain (PYD) is one of the components of the NLRP2 gene. Other components include a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). The products of NLRP2 gene are known to interact with IkB kinase (IKK) complex components. It can also regulate the activities of both caspase-1 and nuc ...
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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 4.0 International License NLRP1 is expressed by a variety of cell types, which are predominantly epithelial or hematopoietic. The expression is also seen within glandular epithelial structures including the lining of the small intestine, stomach, airway epithelia and in hairless or glabrous skin. NLRP1 polymorphisms are associated with skin extra-intestinal manifestations in CD. Its highest expression was detected in human skin, in psoriasis and in vitiligo. Polymorphisms of NLRP1 were found in lupus erythematosus and diabetes type 1. Variants of mouse NLRP1 were found to be activated upon N-terminal cleavage by the protease in anthrax lethal factor. Function This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family ...
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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 interferon activity. Recently, NLRC5 has been suggested to play a positive role in the regulation of Major Histocompatibility Class I (MHCI) molecule expression. This aspect of NLRC5 function was further investigated with the help of ''Nlrc5''- deficient mice, which showed reduced MHCI expression in lymphocytes (particularly T, NK and NKT lymphocytes). In lymphocytes, NLRC5 localizes to the nucleus and drives MHCI gene expression by occupying ''H-2D'' and ''H-2K'' gene promoters. In humans, the NLRC5 protein is encoded by the ''NLRC5'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have seve ...
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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 contains an N-terminal CARD domain, a central nucleotide binding/ NACHT domain, and a C-terminal leucine rich repeat ( LRR) domain. It belongs to a family of NLR proteins that includes the transcriptional co-activator CIITA and the canonical inflammasome protein NLRP3. A truncated murine NLRC4 was the first member of this family whose crystal structure was solved. Function NLRC4 is best associated with triggering formation of the inflammasome. Unlike NLRP3, certain inflammasome-dependent functions of NLRC4 may be carried out independently of the inflammasome scaffold ASC. Human Ced4 homologs include APAF1, NOD1 (CARD4), and NOD2 (CARD15). These proteins have at least 1 N-terminal CARD domain followed by a centrally located nucleotide-bindi ...
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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 containing 3'' (NOD3) and CLR16.2. NLRC3 inhibits the activity of T cells. NLRC3 also inhibits the mTOR The mammalian target of sirolimus, rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MT ... signalling pathway to block cellular proliferation. References LRR proteins NOD-like receptors {{Transmembranereceptor-stub ...
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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'' gene located on chromosome 16. NOD2 plays an important role in the immune system. It recognizes bacterial molecules ( peptidoglycans) and stimulates an immune reaction. NOD2 is an intracellular pattern recognition receptor, which is similar in structure to resistant proteins of plants and recognizes molecules containing the specific structure called muramyl dipeptide (MDP) that is found in certain bacteria. Structure The C-terminal portion of the protein contains a leucine-rich repeat domain that is known to play a role in protein–protein interactions. The middle part of the protein is characterized by a NOD domain involved in protein self-oligomerization. The N-terminal portion contains two CARD domains known to play a role in apo ...
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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 recruitment domain (CARD). NOD1 is a member of NOD-like receptor protein family and is a close relative of NOD2. NOD1 is an intracellular pattern recognition receptor, which is similar in structure to resistant proteins of plants, and mediates innate and acquired immunity by recognizing molecules containing D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety, including bacterial peptidoglycan. Nod1 interacts with RIPK2 through the CARDs of both molecules (See the structure of the NOD1 CARD in the right panel). Stimulation of NOD1 by iE-DAP containing molecules results in activation of the transcription factor NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of D ...
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