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Gene Review

NLRP2  -  NLR family, pyrin domain containing 2

Homo sapiens

Synonyms: CLR19.9, FLJ20510, NACHT, LRR and PYD domains-containing protein 2, NALP2, NBS1, ...
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Disease relevance of NLRP2

  • Two human pancreatic cell lines, PAN1 and BXPC3, expressed gastrin at both the RNA and protein levels and are shown to be representative of human pancreatic adenocarcinomas in terms of gastrin expression [1].
  • We hypothesized that polymorphisms of NBS1 are associated with breast cancer risk [2].
  • Nijmegen breakage syndrome 1 (NBS1) protein is one of the key proteins that participates in recognition and repair of DSBs in humans [2].
  • Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation [3].
  • Although PAN 1 is expressed by gonococci during gonorrhea, the function of the PAN proteins remains unknown [4].

High impact information on NLRP2

  • We showed that Akl1 promotes phosphorylation of Pan1 in this complex and reduces the endocytic ability of the cell, as does Prk1 [5].
  • Gastrin antiserum synergized with both taxotere and gemcitabine in inhibiting the in vitro growth of the PAN1 cell line with the inhibitory effect of the antiserum increasing from 12.7% to 70.2% with taxotere (P < 0.05) and 28.6% with gemcitabine (P < 0.01) after controlling for the effects of the cytotoxics [1].
  • Gastrin antisense-transfected PAN1 cells had increased sensitivity to the antiproliferative effects of both gemcitabine (IC50 of > 100 microg/ml reduced to 0.1 microg/ml) and taxotere (IC50 of 20 microg/ml reduced to < 0.01 microg/ml) when compared with vector controls [1].
  • Both PYPAF2 and PYPAF3 mRNAs are broadly expressed in a variety of tissues; however, neither is expressed in skeletal muscle, and only PYPAF2 mRNA is expressed in heart and brain [6].
  • In gene transfer experiments PAN1 enhances caspase-1 activation and IL-1beta secretion in collaboration with ASC [7].

Biological context of NLRP2

  • In gene transfection studies PAN1 manifests an inhibitory influence on NF-kappaB activation induced by various pro-inflammatory stimuli, including tumor necrosis factor TNFalpha and interleukin-1beta (IL-1beta) [7].
  • Interestingly, the hPAN nuclease complex has a higher substrate specificity to poly(A) RNA upon its association with PABP [8].
  • Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <=55 years [2].
  • These findings imply that heterozygous NBS1 germline mutations may contribute significantly to the overall incidence of NHL, especially of the gastrointestinal tract, in Central Europe. (c) 2006 Wiley-Liss, Inc [3].
  • The frequency of spontaneous chromosome abnormalities in peripheral blood lymphocytes and the X-ray G2 sensitivity in lymphoblastoid cell lines (LCL) have been evaluated in heterozygous subjects from three unrelated Nijmegen Breakage Syndrome (NBS) families, characterised by different mutations in the NBS1 gene [9].

Anatomical context of NLRP2


Associations of NLRP2 with chemical compounds

  • In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter [13].
  • 2. Three peptides isolated from nematodes, AF-1, AF-2 and PAN-1 had mainly inhibitory effects with thresholds of around 1 nM [14].

Physical interactions of NLRP2

  • We also show here that PAN1 binds via its PYRIN domain to ASC, an adapter protein involved in caspase-1 activation [7].

Regulatory relationships of NLRP2

  • Conversely, reducing endogenous levels of PAN1 using small interfering RNA enhanced LPS-induced production of ICAM-1 (intercellular adhesion molecule 1), an NF-kappaB-dependent gene [7].

Other interactions of NLRP2


Analytical, diagnostic and therapeutic context of NLRP2

  • The results of immunofluorescent staining and Western blot analysis showed that NBS1 proteins are phosphorylated after exposure to heat in the nucleus of a normal skin fibroblast cell line (82-6 cells) [11].
  • Although FISH technique detected translocation t(14q;21q) in 4 metaphases, deletion 657del5 in exon 6 of the NBS1 gene associated with NBS in Slavic population was not confirmed [15].


  1. The biological and therapeutic importance of gastrin gene expression in pancreatic adenocarcinomas. Harris, J.C., Gilliam, A.D., McKenzie, A.J., Evans, S.A., Grabowska, A.M., Clarke, P.A., McWilliams, D.F., Watson, S.A. Cancer Res. (2004) [Pubmed]
  2. Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <=55 years. Lu, J., Wei, Q., Bondy, M.L., Li, D., Brewster, A., Shete, S., Yu, T.K., Sahin, A., Meric-Bernstam, F., Hunt, K.K., Singletary, S.E., Ross, M.I., Wang, L.E. Carcinogenesis (2006) [Pubmed]
  3. Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation. Steffen, J., Maneva, G., Pop??awska, L., Varon, R., Mioduszewska, O., Sperling, K. Int. J. Cancer (2006) [Pubmed]
  4. Anaerobic growth of gonococci does not alter their Opa-mediated interactions with human neutrophils. Frangipane, J.V., Rest, R.F. Infect. Immun. (1992) [Pubmed]
  5. Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells. Takahashi, T., Furuchi, T., Naganuma, A. Cancer Res. (2006) [Pubmed]
  6. PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta secretion. Kinoshita, T., Wang, Y., Hasegawa, M., Imamura, R., Suda, T. J. Biol. Chem. (2005) [Pubmed]
  7. PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. Bruey, J.M., Bruey-Sedano, N., Newman, R., Chandler, S., Stehlik, C., Reed, J.C. J. Biol. Chem. (2004) [Pubmed]
  8. Identification of a human cytoplasmic poly(A) nuclease complex stimulated by poly(A)-binding protein. Uchida, N., Hoshino, S., Katada, T. J. Biol. Chem. (2004) [Pubmed]
  9. Chromosome instability and nibrin protein variants in NBS heterozygotes. Tanzanella, C., Antoccia, A., Spadoni, E., di Masi, A., Pecile, V., Demori, E., Varon, R., Marseglia, G.L., Tiepolo, L., Maraschio, P. Eur. J. Hum. Genet. (2003) [Pubmed]
  10. Ca(2+)versus Mg(2+) Coordination at the Nucleotide-binding site of the Sarcoplasmic Reticulum Ca(2+)-ATPase. Picard, M., Jensen, A.M., Sørensen, T.L., Champeil, P., Møller, J.V., Nissen, P. J. Mol. Biol. (2007) [Pubmed]
  11. Heat-induced phosphorylation of NBS1 in human skin fibroblast cells. Ohnishi, K., Scuric, Z., Yau, D., Schiestl, R.H., Okamoto, N., Takahashi, A., Ohnishi, T. J. Cell. Biochem. (2006) [Pubmed]
  12. Association of Ionizing Radiation-Induced Foci of NBS1 with Chromosomal Instability and Breast Cancer Susceptibility. Someya, M., Sakata, K., Tauchi, H., Matsumoto, Y., Nakamura, A., Komatsu, K., Hareyama, M. Radiat. Res. (2006) [Pubmed]
  13. The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells. Watada, H., Kajimoto, Y., Umayahara, Y., Matsuoka, T., Kaneto, H., Fujitani, Y., Kamada, T., Kawamori, R., Yamasaki, Y. Diabetes (1996) [Pubmed]
  14. An initial screen of a series of neuroactive peptides for activity on identified central neurones of Helix aspersa. Pedder, S., Sharma, R., Muneoka, Y., Walker, R.J. Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol. (1992) [Pubmed]
  15. A duplication dup(4)(q28q35.2) de novo in a newborn. Cernakova, I., Kvasnicova, M., Lovasova, Z., Badova, N., Drabek, J., Bouchalova, K., Trojanec, R., Hajduch, M. Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia. (2006) [Pubmed]
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