Nlrp14

NLRPs (acronym for "NIGHT, LRR and PYD domains-containing protein) are, together with the NOD1 and NOD2 proteins, members of the NLR (Nod-like Receptor) protein family and play a major role in innate immunity as pathogen recognition receptors (PPRs). Like the NOD proteins, NLRPs are expressed exclusively cytoplasmically. All NLRPs (they all contain a pyrin domain) are encoded by a common gene family in humans. NLRPs are characterised by their ability to activate different inflammatory complexes.

NLRP14 is a cytosolic protein encoded in humans by the NLRP14 gene located on chromosome 11p15.4.

Inflammasomes are differently composed cytosolic protein complexes, whereby the different NLRPs are of great importance for their functionality. Inflammasomes are predominantly found in immune cells such as dendritic cells and macrophages.

The activation of an inflammasome complex leads to the expression of different caspases, which convert inactive interleukin-1beta and interleukin-18 into their active form.

Most short NLRPs have an N-terminal pyrin domain (PYD), followed by the NIGHT domain, a NIGHT-associated domain (NAD), and a C-terminal leucine-rich region (LRR). NLRP13 has a regulatory function in the innate and adaptive immune system.

Little is known about the mode of action of NLRP14. NLRP14 interacts with nucleic acids via a nucleic acid sensing pathway, where the function of TBK1 (TANK binding kinase 1) is controlled. TBK1 is a kinase that labels target proteins (ubiquitination) and degrades them. A human nonsense mutation of the pathogen recognition receptor 14 leads to a loss of NLRP14 control function and excessive degradation of nucleic acids. The consequence is male sterility (Abe T et al.2017).

1. Abe T et al(2017) Germ-Cell-Specific Inflammasome Component NLRP14 Negatively Regulates Cytosolic Nucleic Acid Sensing to Promote Fertilization. Immunity 46:621-634.
2. Eibl C et al (2014) Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions. Acta Crystallogr D Biol Crystallogr 70:2007-2018.
3. Westerveld GH et al (2006) Mutations in the testis-specific NALP14 genes in men suffering from spermatogenic failure. Hum reprod 21:3178-3184.