Description
NACHT, LRR and PYD domains-containing protein 3 (NALP3), Nucleotide-Binding Oligomerization Domain, or Leucine Rich Repeat and Pyrin Domain Containing 3 (NLRP3) (human NLRP3-isoform 2 theoretical molecular weight 118kDa) acts as a cytosolic receptor for stress-signals initiated by a wide variety of pathogen-associated molecular patterns (
PAMPS) and danger-associated molecular patterns (
DAMPs) (1).
NLRP3 belongs to the family of NOD-like receptors, a type of pattern-recognition receptor (PRR) which participates in
innate immune responses. The exact mechanisms leading to NLRP3 activation are still not fully resolved. Some proposed mechanisms for NLRP3 inflammasome activation include induced ion channel flux as exemplified by potassium efflux, sodium influx and calcium signaling, generation of
mitochondrial reactive oxygen species (ROS), and
lysosomal destabilization (2). Activation of NLRP3 induces its association with the adaptor protein Apoptosis-associated Speck-like protein containing CARD (
ASC) forming a complex that binds to
Caspase-1 (1, 2). The inflammasome complex, comprised of NLRP3, ASC and Caspase 1, induces the processing of pro-IL-1beta and pro-IL-18 and release of the mature inflammatory cytokines
IL-1beta and
IL-18 and
pyroptosis (1-3).
NLRP3 is expressed in a variety of cell types such as monocytes,
dendritic cells, lymphocytes and
epithelial cells (3). Abnormal NLRP3 activation may occur as the result of inherited mutations and is associated with diseases such as hereditary periodic fevers (HPFs) and familial cold autoinflammatory syndrome (FCAS). Additionally, abnormal NLRP3 activation is associated with a variety of diseases such as gout, obesity, atherosclerosis,
Alzheimers, multiple sclerosis and
type 2 diabetes (1, 3). NLRP3 inflammasome is regulated by several post-translational modifications (e.g., ubiquitination, phosphorylation and sumoylation) as well as by various interacting proteins (e.g.,
JNK1,
FBXO3,
TXNIP,
MARK4 and PKD) (4).
References
1. Abderrazak, A., Syrovets, T., Couchie, D., El Hadri, K., Friguet, B., Simmet, T., & Rouis, M. (2015). NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biology. https://doi.org/10.1016/j.redox.2015.01.008
2. Yang, Y., Wang, H., Kouadir, M., Song, H., & Shi, F. (2019). Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death and Disease. https://doi.org/10.1038/s41419-019-1413-8
3. Zahid, A., Li, B., Kombe, A. J. K., Jin, T., & Tao, J. (2019). Pharmacological inhibitors of the nlrp3 inflammasome. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2019.02538
4. Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019). The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms20133328
Bioinformatics
Uniprot |
Human Human Human Human Human Human |
Product By Gene ID |
114548 |
Alternate Names |
- AII
- AII/AVP
- Angiotensin/vasopressin receptor AII/AVP-like
- AVP
- C1orf7
- Caterpiller protein 1.1
- CLR1.1
- Cold autoinflammatory syndrome 1 protein
- Cold autoinflammatory syndrome 1
- Cryopyrin
- Familial cold autoinflammatory syndrome
- FCU
- Leucine-rich repeat-, and PYD-containing protein 3
- Muckle-Wells syndrome
- MWS
- NACHT, LRR and PYD containing protein 3
- NACHT, LRR and PYD domains-containing protein 3
- NALP3
- NLR family, pyrin domain containing 3
- NLRP3
- Nucleotide-Binding Oligomerization Domain, Leucine Rich Repeat And Pyrin Domain Containing 3
- PYPAF1
- PYRIN-containing APAF1-like protein 1
|