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Gene Review

NLRP1  -  NLR family, pyrin domain containing 1

Homo sapiens

Synonyms: CARD7, CIDED, CLR17.1, Caspase recruitment domain-containing protein 7, DEFCAP, ...
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Disease relevance of NLRP1


Psychiatry related information on NLRP1


High impact information on NLRP1

  • Like the structurally related apoptotic protease-activating factor-1 (APAF-1), which is responsible for the activation of caspase-9, the NALP1 protein forms a large, signal-induced multiprotein complex, the inflammasome, resulting in the activation of pro-inflammatory caspases [7].
  • The NALP3 protein is homologous to NALP1, which is a component of the inflammasome, a molecular platform that activates the proinflammatory caspases-1 and -5 [8].
  • Several genes related to nitrogen metabolism, especially those regulated by the NtrC and NAC proteins and transcribed via the varsigma(54) alternative sigma factor, were suppressed by both normal and oxidase-deficient neutrophils [9].
  • These data unveil another level of complexicity in the regulation of intracellular innate immunity and may have important implications for the molecular understanding of NOD/NALP protein-driven disease pathophysiology [10].
  • The recent determination of the DNA and protein binding NAC domain structure offers insight into the molecular functions of the protein family [11].

Chemical compound and disease context of NLRP1


Biological context of NLRP1

  • Also described here are studies on the mechanism of action studies including deletion analyses and investigations of nucleotide binding, which begin to elucidate a regulatory function for NALP1 in neuronal apoptosis [1].
  • We report here that NALP1 gene expression was induced in primary cerebellar granule neurons (CGN) upon injury [1].
  • Expression of recombinant NALP1 stimulated cell death in both HeLa cells and CGN by an apoptotic mechanism, demonstrated by the induction of apoptotic nuclear morphology and activation of the apoptotic enzyme caspase-3 [1].
  • Conditional logistic-regression analysis of NALP1 SNPs indicated that at least two variants contribute independently to the risk of disease [4].
  • Fine-scale association mapping with the use of DNA from affected families and additional SNPs in and around NALP1 showed an association of specific variants with vitiligo alone, with an extended autoimmune and autoinflammatory disease phenotype, or with both [4].

Anatomical context of NLRP1

  • We investigated the biological consequence of over-expression of NALP1 in both HeLa cells and in CGN [1].
  • RESULTS: Association analyses resulted in our identifying as a candidate gene NALP1, which encodes NACHT leucine-rich-repeat protein 1, a regulator of the innate immune system [4].
  • In the present study, we report that expression of NALP1 is absent from CD34+ haematopoietic blast cells, and its levels are upregulated upon differentiation of CD34+ cells into granulocytes and to a lesser extent into monocytes [3].
  • In peripheral blood cells, the highest levels of NALP1 were observed in CD3+ (T-lymphocytes), CD15+ (granulocytes) and CD14+ (monocytes) cell populations [3].
  • Thus NALP1 is transcriptionally regulated by CREB in myeloid cells, a mechanism that may contribute to modulate the response of these cells to pro-inflammatory stimuli [3].

Associations of NLRP1 with chemical compounds

  • A certain class of the NAC transcription factors is important for growth suppression at the boundary, and auxin and microRNAs participate in boundary formation by regulating NAC gene expression [15].
  • MGO and cisplatin increased PKCdelta activity by 4-fold, and this effect was blocked by the PKCdelta inhibitor rottlerin but not by NAC [16].
  • Mangiferin, similar to the other known antioxidants, NAC and PDTC, inhibits TNF-induced reactive oxygen intermediate (ROI) generation [17].
  • Exposure to NAC fibrils increased also the nuclear translocation of nuclear factor kappa B (NF-kappaB) and enhanced its DNA-binding activity, which was inhibited by PG and BPN more efficiently in neurons than in astrocytes [12].
  • NAC and alpha-synuclein both form beta-sheet structures upon ageing, aggregate to form fibrils, and are neurotoxic [5].

Other interactions of NLRP1

  • Recently, the 3D structures determined by NMR of NALP1 and ASC PAAD domain, members of the PAAD family, have shown that it is composed of a 6 helix bundle as with other death domain family members [18].
  • Further, a transition from complete disorder to order of the alpha2-alpha3 loop upon binding, as suggested for NALP1, is unlikely to be a common attribute of pyrin domain interactions [19].
  • NALP1 is a transcriptional target for cAMP-response-element-binding protein (CREB) in myeloid leukaemia cells [3].

Analytical, diagnostic and therapeutic context of NLRP1

  • The duration of pain relief following NALP (59.65 +/- 68.72 days) was significantly longer compared with that recorded following electrical stimulation (2.97 +/- 2.58 days) [20].
  • Circular dichroism and infrared spectroscopies suggested that the OPR, R5, and Q50 motifs formed an antiparallel beta sheet as well as a random coil, whereas the R2 and NAC motifs mainly formed random coils [21].
  • We examined the interactions between apoE and NAC and found that apoE bound synthetic NAC, forming a complex that resisted reducing agents and separation on SDS-PAGE [22].
  • Less hair cell loss was also observed in the ALCAR and NAC groups than in the control group [14].


  1. Expression of NALP1 in cerebellar granule neurons stimulates apoptosis. Liu, F., Lo, C.F., Ning, X., Kajkowski, E.M., Jin, M., Chiriac, C., Gonzales, C., Naureckiene, S., Lock, Y.W., Pong, K., Zaleska, M.M., Jacobsen, J.S., Silverman, S., Ozenberger, B.A. Cell. Signal. (2004) [Pubmed]
  2. Genetic differentiation of appendiceal tumor malignancy: a guide for the perplexed. Modlin, I.M., Kidd, M., Latich, I., Zikusoka, M.N., Eick, G.N., Mane, S.M., Camp, R.L. Ann. Surg. (2006) [Pubmed]
  3. NALP1 is a transcriptional target for cAMP-response-element-binding protein (CREB) in myeloid leukaemia cells. Sanz, C., Calasanz, M.J., Andreu, E., Richard, C., Prosper, F., Fernandez-Luna, J.L. Biochem. J. (2004) [Pubmed]
  4. NALP1 in vitiligo-associated multiple autoimmune disease. Jin, Y., Mailloux, C.M., Gowan, K., Riccardi, S.L., LaBerge, G., Bennett, D.C., Fain, P.R., Spritz, R.A. N. Engl. J. Med. (2007) [Pubmed]
  5. Identification of the region of non-Abeta component (NAC) of Alzheimer's disease amyloid responsible for its aggregation and toxicity. Bodles, A.M., Guthrie, D.J., Greer, B., Irvine, G.B. J. Neurochem. (2001) [Pubmed]
  6. Synuclein proteins and Alzheimer's disease. Brookes, A.J., St Clair, D. Trends Neurosci. (1994) [Pubmed]
  7. NALPs: a novel protein family involved in inflammation. Tschopp, J., Martinon, F., Burns, K. Nat. Rev. Mol. Cell Biol. (2003) [Pubmed]
  8. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Agostini, L., Martinon, F., Burns, K., McDermott, M.F., Hawkins, P.N., Tschopp, J. Immunity (2004) [Pubmed]
  9. mRNA expression profiles for Escherichia coli ingested by normal and phagocyte oxidase-deficient human neutrophils. Staudinger, B.J., Oberdoerster, M.A., Lewis, P.J., Rosen, H. J. Clin. Invest. (2002) [Pubmed]
  10. A short isoform of NOD2/CARD15, NOD2-S, is an endogenous inhibitor of NOD2/receptor-interacting protein kinase 2-induced signaling pathways. Rosenstiel, P., Huse, K., Till, A., Hampe, J., Hellmig, S., Sina, C., Billmann, S., von Kampen, O., Waetzig, G.H., Platzer, M., Seegert, D., Schreiber, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. NAC transcription factors: structurally distinct, functionally diverse. Olsen, A.N., Ernst, H.A., Leggio, L.L., Skriver, K. Trends Plant Sci. (2005) [Pubmed]
  12. Generation of reactive oxygen species and activation of NF-kappaB by non-Abeta component of Alzheimer's disease amyloid. Tanaka, S., Takehashi, M., Matoh, N., Iida, S., Suzuki, T., Futaki, S., Hamada, H., Masliah, E., Sugiura, Y., Ueda, K. J. Neurochem. (2002) [Pubmed]
  13. TNFalpha induces chromosomal abnormalities independent of ROS through IKK, JNK, p38 and caspase pathways. Higashimoto, T., Panopoulos, A., Hsieh, C.L., Zandi, E. Cytokine (2006) [Pubmed]
  14. Prevention of impulse noise-induced hearing loss with antioxidants. Kopke, R., Bielefeld, E., Liu, J., Zheng, J., Jackson, R., Henderson, D., Coleman, J.K. Acta Otolaryngol. (2005) [Pubmed]
  15. Genetic control of shoot organ boundaries. Aida, M., Tasaka, M. Curr. Opin. Plant Biol. (2006) [Pubmed]
  16. Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase Cdelta. Godbout, J.P., Pesavento, J., Hartman, M.E., Manson, S.R., Freund, G.G. J. Biol. Chem. (2002) [Pubmed]
  17. beta-D-Glucoside suppresses tumor necrosis factor-induced activation of nuclear transcription factor kappaB but potentiates apoptosis. Sarkar, A., Sreenivasan, Y., Ramesh, G.T., Manna, S.K. J. Biol. Chem. (2004) [Pubmed]
  18. Thermodynamics and stability of the PAAD/DAPIN/PYRIN domain of IFI-16. Dalal, K., Pio, F. FEBS Lett. (2006) [Pubmed]
  19. Structure and Dynamics of ASC2, a Pyrin Domain-only Protein That Regulates Inflammatory Signaling. Natarajan, A., Ghose, R., Hill, J.M. J. Biol. Chem. (2006) [Pubmed]
  20. Relief of cancer pain in man: alcohol-induced neuroadenolysis vs. electrical stimulation of the pituitary gland. Yanagida, H., Corssen, G., Trouwborst, A., Erdmann, W. Pain (1984) [Pubmed]
  21. The effects of aggregation-inducing motifs on amyloid formation of model proteins related to neurodegenerative diseases. Tanaka, M., Machida, Y., Nishikawa, Y., Akagi, T., Morishima, I., Hashikawa, T., Fujisawa, T., Nukina, N. Biochemistry (2002) [Pubmed]
  22. Isoform-specific binding of human apolipoprotein E to the non-amyloid beta component of Alzheimer's disease amyloid. Olesen, O.F., Mikkelsen, J.D., Gerdes, C., Jensen, P.H. Brain Res. Mol. Brain Res. (1997) [Pubmed]
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