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NLRP12

Summary

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
Available structures
PDBOrtholog search: PDBe RCSB
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 HomoloGene: 16972 GeneCards: NLRP12
Orthologs
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

NLRP Structure edit

NLRPs, or NALPs, are cytoplasmic innate immune sensors that form a subfamily within the larger CATERPILLER protein family. Most short NLRP proteins, including NLRP12, have 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), also has a C-terminal extension containing a function to find domain (FIIND) and a caspase recruitment domain (CARD). Some NLRPs, including NLRP12, are implicated in the activation of proinflammatory caspases (e.g., CASP1; MIM 147678) via their involvement in multiprotein complexes called inflammasomes in context-dependent manners (Tschopp et al., 2003).[supplied by OMIM][7]

NLRP12 Function and Pathology edit

NLRP12 is an innate immune cytosolic sensor and signaling molecule linked to several infections and inflammatory disorders.[8] It can form multimeric protein cell death complexes known as inflammasomes and PANoptosomes in response to specific stimuli.[9][10][11][12] NLRP12 has been reported as both a positive and negative regulator of immune signaling in context-dependent manners.[13][14][15] Infection with certain pathogens, such as Yersinia pestis or Plasmodium chabaudi, activates the NLRP12 inflammasome to release the inflammatory cytokines IL-1β and IL-18, which may help protect against severe infection.[8][10][11][12] However, NLRP12 acts as a negative regulator of the NF-kB and MAPK signaling pathways following infection with Salmonella enterica serovar Typhimurium, vesicular stomatitis virus, Klebsiella pneumoniae, or Mycobacterium tuberculosis, and in certain malignancies.[8][16] NLRP12 also inhibits signaling in T cells, which is linked to reduced atypical neuroinflammation and atopic dermatitis in mouse models.[17] NLRP12 has also been identified as an innate immune sensor that triggers inflammatory cell death, PANoptosis, and pathology when heme is combined with specific components of cellular injury or infection.[11][12] This combination enables NLRP12 to assemble the NLRP12-PANoptosome and trigger cell death via caspase-8 and RIPK3. NLRP12 expression is also elevated in patients with hemolytic diseases such as sickle cell disease and malaria, as well as infections such as SARS-CoV-2, influenza, and bacterial pneumonia.[18][19] Deletion of Nlrp12 protects against pathology in animal models of hemolytic disease.[11][12]

References edit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000142405 – Ensembl, May 2017
  2. ^ a b c 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. ^ Tschopp J, Martinon F, Burns K (Feb 2003). "NALPs: a novel protein family involved in inflammation". Nat Rev Mol Cell Biol. 4 (2): 95–104. doi:10.1038/nrm1019. PMID 12563287. S2CID 31417018.
  6. ^ Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J (Aug 2002). "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing". J Biol Chem. 277 (33): 29874–80. doi:10.1074/jbc.M203915200. PMID 12019269.
  7. ^ a b "Entrez Gene: NLRP12 NLR family, pyrin domain containing 12".
  8. ^ a b c Tuladhar S, Kanneganti T (2020). "NLRP12 in innate immunity and inflammation". Molecular Aspects of Medicine. 76. doi:10.1016/j.mam.2020.100887. PMC 9375713. PMID 32838963.
  9. ^ "The NLRP12 Inflammasome Recognizes Yersinia pestis". Immunity.
  10. ^ a b Ataide MA, Andrade WA, Zamboni DS, Wang D, Souza Md, Franklin BS, Elian S, Martins FS, Pereira D, Reed G, Fitzgerald KA, Golenbock DT, Gazzinelli RT (2014-01-16). 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. ISSN 1553-7374. PMC 3894209. PMID 24453977.
  11. ^ a b c d Sundaram B, Pandian N, Mall R, Wang Y, Sarkar R, Kim HJ (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.
  12. ^ a b c d "St. Jude finds NLRP12 as a new drug target for infection, inflammation and hemolytic diseases". www.stjude.org. Retrieved 2024-02-20.
  13. ^ Pinheiro AS, Eibl C, Ekman-Vural Z, Schwarzenbacher R, Peti W (2011-11-04). "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. ISSN 0022-2836. PMC 3202057. PMID 21978668.
  14. ^ Tuncer S, Fiorillo MT, Sorrentino R (2014-09-23). "The multifaceted nature of NLRP12". Journal of Leukocyte Biology. 96 (6): 991–1000. doi:10.1189/jlb.3RU0514-265RR. ISSN 0741-5400. PMID 25249449. S2CID 30257891.
  15. ^ Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, Distefano PS, Bertin J (2002). "PYPAF7, a Novel PYRIN-containing Apaf1-like Protein That Regulates Activation of NF-κB and Caspase-1-dependent Cytokine Processing". Journal of Biological Chemistry. 277 (33): 29874–29880. doi:10.1074/jbc.M203915200. PMID 12019269.
  16. ^ Allen IC, Wilson JE, Schneider M, Lich JD, Roberts RA, Arthur JC, Woodford RM, Davis BK, Uronis JM, Herfarth HH, Jobin C, Rogers AB, Ting JP (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.
  17. ^ Lukens JR, Gurung P, Shaw PJ, Barr MJ, Zaki MH, Brown SA, Vogel P, Chi H, Kanneganti TD (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.
  18. ^ Parnell GP, McLean AS, Booth DR, Armstrong NJ, Nalos M, Huang SJ, Manak J, Tang W, Tam OY, Chan S, Tang BM (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. ISSN 1364-8535. 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.

Further reading edit

  • Shami PJ, Kanai N, Wang LY, et al. (2001). "Identification and characterization of a novel gene that is upregulated in leukaemia cells by nitric oxide". Br. J. Haematol. 112 (1): 138–47. doi:10.1046/j.1365-2141.2001.02491.x. PMID 11167794. S2CID 44981142.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Williams KL, Taxman DJ, Linhoff MW, et al. (2003). "Cutting edge: Monarch-1: a pyrin/nucleotide-binding domain/leucine-rich repeat protein that controls classical and nonclassical MHC class I genes". J. Immunol. 170 (11): 5354–8. doi:10.4049/jimmunol.170.11.5354. PMID 12759408.
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Williams KL, Lich JD, Duncan JA, et al. (2006). "The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals". J. Biol. Chem. 280 (48): 39914–24. doi:10.1074/jbc.M502820200. PMC 4422647. PMID 16203735.
  • Lich JD, Williams KL, Moore CB, et al. (2007). "Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes". J. Immunol. 178 (3): 1256–60. doi:10.4049/jimmunol.178.3.1256. PMID 17237370.
  • Arthur JC, Lich JD, Aziz RK, et al. (2007). "Heat shock protein 90 associates with monarch-1 and regulates its ability to promote degradation of NF-kappaB-inducing kinase". J. Immunol. 179 (9): 6291–6. doi:10.4049/jimmunol.179.9.6291. PMID 17947705.
  • Chen L, Wilson JE, Koenigsknecht MJ, et al. (2017). "NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth". Nature Immunology. 18 (5): 541–551. doi:10.1038/ni.3690. PMC 5395345. PMID 28288099.