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NLRP12

From Wikipedia, the free encyclopedia

NLRP12
Identifiers
AliasesNLRP12, CLR19.3, FCAS2, NALP12, PAN6, PYPAF7, RNO, RNO2, NLR family, pyrin domain containing 12, NLR family pyrin domain containing 12
External IDsOMIM: 609648; MGI: 2676630; GeneCards: NLRP12
Available structures
PDBOrtholog search: PDBe RCSB
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

91662

378425

Ensembl

ENSG00000142405

ENSMUSG00000078817

UniProt

P59046

E9Q5R7

RefSeq (mRNA)

NM_001277126
NM_001277129
NM_033297
NM_144687

NM_001033431

RefSeq (protein)

NP_001264055
NP_001264058
NP_653288

NP_001028603

Location (UCSC)Chr 19: 53.79 – 53.82 MbChr 7: 3.27 – 3.3 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

NOD-like receptor|Nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain (PYD)-containing protein 12 (NLRP12; also known as NACHT, LRR and PYD domains-containing protein 12 or NALP12) is a protein that in humans is encoded by the NLRP12 gene.[5][6][7]

NLRP12 is a cytoplasmic innate immune sensor belonging to the NLRP (NALP) subfamily of the larger CATERPILLER protein family. It participates in regulation of inflammatory signaling and may promote assembly of multiprotein signaling complexes including inflammasomes and PANoptosomes in a context-dependent manner.[5][8]

Structure

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NLRPs, or NALPs, are cytoplasmic innate immune sensors that form a subfamily within the larger CATERPILLER protein family. Most short NLRP proteins, including NLRP12, contain 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), additionally contains a function to find domain (FIIND) and a caspase recruitment domain (CARD).[5]

Function

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NLRP12 functions as an innate immune cytosolic sensor and signaling molecule.[8] It has been reported to act as both a positive and negative regulator of immune signaling depending on cellular and pathogenic context.[9][10][6]

Some NLRPs, including NLRP12, are implicated in activation of proinflammatory caspases such as CASP1 through their participation in multiprotein inflammasome complexes.[5] [supplied by OMIM].[7]

NLRP12 can form multimeric protein signaling and cell death complexes including inflammasomes and PANoptosomes in response to specific stimuli.[11][12][13]

In response to pathogens including Yersinia pestis and Plasmodium chabaudi, NLRP12 inflammasome activation promotes release of inflammatory cytokines IL-1β and IL-18, contributing to host defense.[8][12][13]

NLRP12 also negatively regulates NF-kB and MAPK signaling pathways following infection with Salmonella enterica serovar Typhimurium, vesicular stomatitis virus, Klebsiella pneumoniae, and Mycobacterium tuberculosis.[8][14]

NLRP12 additionally inhibits signaling in T cells and has been linked to modulation of inflammatory responses.[15]

Clinical significance

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NLRP12 has been linked to infectious, inflammatory, and malignant conditions.[8]

NLRP12 has been identified as an innate immune sensor that can trigger inflammatory cell death through PANoptosis, a lytic cell death pathway mediated through PANoptosomes and coordinated activity of caspases and receptor-interacting protein kinases (RIPKs).[13][16]

Through activation of PANoptosis, NLRP12 has been implicated in pathology associated with heme exposure combined with infection or tissue injury.[13] This process enables assembly of the NLRP12-PANoptosome and induction of cell death through caspase-8 and RIPK3. NLRP12 can additionally cooperate with other NLR proteins, including NLRC5 and NLRP3, in response to NAD+ depletion.[16][17]

Expression of NLRP12 is elevated in hemolytic diseases including sickle cell disease and malaria and in infections including SARS-CoV-2, influenza, and bacterial pneumonia.[18][19]

Deletion of Nlrp12 protects against pathology in animal models of hemolytic disease.[13]

References

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  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000142405 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000078817 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 4 Tschopp J, Martinon F, Burns K (February 2003). "NALPs: a novel protein family involved in inflammation". Nature Reviews. Molecular Cell Biology. 4 (2): 95–104. doi:10.1038/nrm1019. PMID 12563287. S2CID 31417018.
  6. 1 2 Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, et al. (August 2002). "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing". The Journal of Biological Chemistry. 277 (33): 29874–29880. doi:10.1074/jbc.M203915200. PMID 12019269.
  7. 1 2 "Entrez Gene: NLRP12 NLR family, pyrin domain containing 12".
  8. 1 2 3 4 5 Tuladhar S, Kanneganti T (2020). "NLRP12 in innate immunity and inflammation". Molecular Aspects of Medicine. 76 100887. doi:10.1016/j.mam.2020.100887. PMC 9375713. PMID 32838963.
  9. ↑ Pinheiro AS, Eibl C, Ekman-Vural Z, Schwarzenbacher R, Peti W (November 2011). "The NLRP12 pyrin domain: structure, dynamics, and functional insights". Journal of Molecular Biology. 413 (4): 790–803. doi:10.1016/j.jmb.2011.09.024. PMC 3202057. PMID 21978668.
  10. ↑ Tuncer S, Fiorillo MT, Sorrentino R (December 2014). "The multifaceted nature of NLRP12". Journal of Leukocyte Biology. 96 (6): 991–1000. doi:10.1189/jlb.3RU0514-265RR. PMID 25249449. S2CID 30257891.
  11. ↑ Vladimer GI, Weng D, Paquette SW, Vanaja SK, Rathinam VA, Aune MH, et al. (2012). "The NLRP12 Inflammasome Recognizes Yersinia pestis". Immunity. 37 (1): 96–107. doi:10.1016/j.immuni.2012.07.006. PMC 3753114. PMID 22840842.
  12. 1 2 Ataide MA, Andrade WA, Zamboni DS, Wang D, Souza MD, Franklin BS, et al. (January 2014). Sibley LD (ed.). "Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection". PLoS Pathogens. 10 (1) e1003885. doi:10.1371/journal.ppat.1003885. PMC 3894209. PMID 24453977.
  13. 1 2 3 4 5 Malireddi RK (June 2023). "NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs". Cell. 186 (13): 2783–2801.e20. doi:10.1016/j.cell.2023.05.005. PMC 10330523. PMID 37267949.
  14. ↑ Allen IC, Wilson JE, Schneider M, Lich JD, Roberts RA, Arthur JC, et al. (2012). "NLRP12 Suppresses Colon Inflammation and Tumorigenesis through the Negative Regulation of Noncanonical NF-κB Signaling". Immunity. 36 (5): 742–754. doi:10.1016/j.immuni.2012.03.012. PMC 3658309. PMID 22503542.
  15. ↑ Lukens JR, Gurung P, Shaw PJ, Barr MJ, Zaki MH, Brown SA, et al. (2015). "The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells". Immunity. 42 (4): 654–664. doi:10.1016/j.immuni.2015.03.006. PMC 4412374. PMID 25888258.
  16. 1 2 St. Jude Children's Research Hospital (2024-06-14). "St. Jude scientists solve decades long mystery of NLRC5 sensor function in cell death and disease". www.stjude.org. Retrieved 2024-08-13.
  17. ↑ Sundaram B, Pandian N, Kim HJ, Abdelaal HM, Mall R, Indari O, et al. (July 2024). "NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation". Cell. 187 (15): 4061–4077.e17. doi:10.1016/j.cell.2024.05.034. PMC 11283362. PMID 38878777.
  18. ↑ Parnell GP, McLean AS, Booth DR, Armstrong NJ, Nalos M, Huang SJ, et al. (August 2012). "A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia". Critical Care. 16 (4) R157. doi:10.1186/cc11477. PMC 3580747. PMID 22898401.
  19. ↑ Tweedell RE, Kanneganti T (2023). "NLRP12-PANoptosome in haemolytic, infectious and inflammatory diseases". Clinical and Translational Medicine. 13 (9) e1409. doi:10.1002/ctm2.1409. PMC 10497829. PMID 37700491.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Further reading

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