NOD2
Encyclopedia
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. Mutations in NOD2 are associated with autoimmune diseases.
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
.
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 domain
s known to play a role in apoptosis
and NF-κB activation pathways.
/Apaf-1 family (also known as NOD-like receptor family) and encodes a protein with two caspase recruitment domains (CARDs) and eleven leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response by recognizing the bacterial molecules which possess the muramyl dipeptide
(MDP) moiety and activating the NF-κB protein. and graft-versus-host disease.
and Blau syndrome
. and graft-versus-host disease.
The NOD2 gene is linked to inflammatory diseases such as inflammatory bowel disease
/Crohn's Disease
and Blau syndrome
.
.
NOD2 has also been shown to bind to MAVS
in response to ssRNA or viral RNA treatment and activate the IFN response. This is the first report of NOD2 acting as a pattern-recognition receptor for viruses.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the NOD2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
located on chromosome 16
Chromosome 16 (human)
125px|rightChromosome 16 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 16 spans about 90 million base pairs and represents just under 3 % of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
. NOD2 plays an important role in the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. It recognizes bacterial molecules (peptidoglycans) and stimulates an immune reaction. Mutations in NOD2 are associated with autoimmune diseases.
NOD2 is an intracellular pattern recognition receptor
Pattern recognition receptor
Pattern recognition receptors are a primitive part of the immune system. They are proteins expressed by cells of the innate immune system to identify pathogen-associated molecular patterns , which are associated with microbial pathogens or cellular stress, as well as damage-associated molecular...
, which is similar in structure to resistant proteins of plants and recognizes molecules containing the specific structure called muramyl dipeptide
Muramyl dipeptide
Muramyl dipeptide is a peptidoglycan constituent of both Gram positive and Gram negative bacteria. It is composed of N-acetylmuramic acid linked by its lactic acid moiety to the N-terminus of an L-alanine D-isoglutamine dipeptide.-See also:* Dipeptide...
(MDP) that is found in certain bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
.
Structure
The C-terminal portion of the protein contains a leucine-rich repeatLeucine-rich repeat
A leucine-rich repeat 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...
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 domain
CARD domain
Caspase recruitment domains, or Caspase activation and recruitment domains , are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct...
s known to play a role in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
and NF-κB activation pathways.
Function
This gene is a member of the NOD1NOD1
Nucleotide-binding oligomerization domain-containing protein 1 is a protein receptor that in humans is encoded by the NOD1 gene. It recognizes bacterial molecules and stimulates an immune reaction....
/Apaf-1 family (also known as NOD-like receptor family) and encodes a protein with two caspase recruitment domains (CARDs) and eleven leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response by recognizing the bacterial molecules which possess the muramyl dipeptide
Muramyl dipeptide
Muramyl dipeptide is a peptidoglycan constituent of both Gram positive and Gram negative bacteria. It is composed of N-acetylmuramic acid linked by its lactic acid moiety to the N-terminus of an L-alanine D-isoglutamine dipeptide.-See also:* Dipeptide...
(MDP) moiety and activating the NF-κB protein. and graft-versus-host disease.
Clinical significance
Mutations in this gene have been associated with Crohn's diseaseCrohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
and Blau syndrome
Blau syndrome
Blau syndrome is characterized by familial granulomatous arthritis, iritis, and skin granulomas, comprising an autosomal dominantly inherited syndrome that overlaps both sarcoidosis and granuloma annulare....
. and graft-versus-host disease.
The NOD2 gene is linked to inflammatory diseases such as inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
/Crohn's Disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
and Blau syndrome
Blau syndrome
Blau syndrome is characterized by familial granulomatous arthritis, iritis, and skin granulomas, comprising an autosomal dominantly inherited syndrome that overlaps both sarcoidosis and granuloma annulare....
.
Interactions
NOD2 has been shown to interact with NLRC4NLRC4
NLR family CARD domain-containing protein 4 is a protein that in humans is encoded by the NLRC4 gene.-Interactions:NLRC4 has been shown to interact with caspase 1 and NOD2.-Further reading:...
.
NOD2 has also been shown to bind to MAVS
VISA (gene)
Mitochondrial antiviral-signaling protein is a protein that in humans is encoded by the MAVS gene. The protein is also known by the names VISA, IPS-1 and Cardif. Aggregated MAVS form protease resistant prion-like aggregates that activate IRF3 dimerization. - NCBI Refseq summary of MAVS :-Further...
in response to ssRNA or viral RNA treatment and activate the IFN response. This is the first report of NOD2 acting as a pattern-recognition receptor for viruses.