NLRP12
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]
NLRP Structure
NLRPs, or NALPs, are
NLRP12 Function and Pathology
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
- ^ a b c GRCh38: Ensembl release 89: ENSG00000142405 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000078817 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 31417018.
- PMID 12019269.
- ^ a b "Entrez Gene: NLRP12 NLR family, pyrin domain containing 12".
- ^ PMID 32838963.
- ^ "The NLRP12 Inflammasome Recognizes Yersinia pestis". Immunity.
- ^ PMID 24453977.
- ^ PMID 37267949.
- ^ 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.
- PMID 21978668.
- S2CID 30257891.
- PMID 12019269.
- PMID 22503542.
- PMID 25888258.
- PMID 22898401.
- PMID 37700491.
Further reading
- 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. 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. 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. 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. 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. 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. 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. 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. 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. PMID 28288099.
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