Alternative titles; symbols
HGNC Approved Gene Symbol: NLRP14
Cytogenetic location: 11p15.4 Genomic coordinates (GRCh38) : 11:7,020,446-7,090,900 (from NCBI)
NALPs are cytoplasmic proteins that form a subfamily within the larger CATERPILLER protein family. Most short NALPs, such as NALP14, have an N-terminal pyrin (MEFV; 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 (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; 147678) via their involvement in multiprotein complexes called inflammasomes (Tschopp et al., 2003).
Tschopp et al. (2003) stated that the 993-amino acid NALP14 protein has the typical PYD-NACHT-LRR domain structure found in the NALP family. Inohara and Nunez (2003) also reported the NALP14 gene, which they called NOD5.
By database and experimental analyses, Yin et al. (2020) found that Nlrp14 was expressed only in mouse testis and ovary, with 2 transcripts.
Tschopp et al. (2003) stated that the NALP14 gene maps to chromosome 11p15.4.
Yin et al. (2020) identified Nlrp14 as a key regulator for differentiation of mouse embryonic stem cells (ESCs) to primordial germ cell-like cells (PGCLCs). Nlrp14 expression was significantly induced during PGCLC differentiation, and Nlrp14 knockdown impaired PGCLC differentiation.
Yin et al. (2020) found that Nlrp14 -/- mice were born at the normal mendelian ratio with no obvious developmental defects. However, female Nlrp1 -/- mice were 100% sterile, despite normal-looking ovaries, and only a few males sired offspring. No difference was observed for overall appearance and gonad-somatic index for Nlrp14 -/- testis compared with controls, but mature spermatozoa in seminiferous tubules of mutant males was substantially decreased due to increased apoptosis. Moreover, both sperm count and motility were significantly reduced, and a substantially higher percentage of Nlrp14 -/- sperm displayed abnormal morphology. Sperm motility was mostly restored when stimulated with human tubal fluid. Further analysis indicated that differentiation of spermatogonial stem cells and meiosis were compromised in Nlrp14 -/- mice. Nlrp14 interacted with Hspa2 (140560), and Nlrp14, Hspa2 and Bag2 (603882) formed a complex that protected Hspa2 from proteasomal degradation by inhibiting its ubiquitination in spermatogonial stem cells. Stabilization of Hspa2 promoted its nuclear translocation for facilitation of spermatid biogenesis. Formation of the NLRP14-HSPA2-BAG2 complex was also detected in human cells, suggesting a conserved function of NLRP14 in human.
Inohara, N., Nunez, G. NODs: intracellular proteins involved in inflammation and apoptosis. Nature Rev. Immun. 3: 371-382, 2003. [PubMed: 12766759] [Full Text: https://doi.org/10.1038/nri1086]
Tschopp, J., Martinon, F., Burns, K. NALPs: a novel protein family involved in inflammation. Nature Rev. Molec. Cell Biol. 4: 95-104, 2003. [PubMed: 12563287] [Full Text: https://doi.org/10.1038/nrm1019]
Yin, Y., Cao, S., Fu, H., Fan, X., Xiong, J., Huang, Q., Liu, Y., Xie, K., Meng, T. G., Liu, Y., Tang, D., Yang, T., and 10 others. A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis. Proc. Nat. Acad. Sci. 117: 22237-22248, 2020. [PubMed: 32839316] [Full Text: https://doi.org/10.1073/pnas.2005533117]