NLRP2
Identifiers
AliasesNLRP2, CLR19.9, NALP2, NBS1, PAN1, PYPAF2, NLR family, pyrin domain containing 2, NLR family pyrin domain containing 2
External IDsOMIM: 609364 MGI: 3041206 HomoloGene: 56789 GeneCards: NLRP2
Orthologs
SpeciesHumanMouse
Entrez

55655

232827

Ensembl

ENSMUSG00000035177

UniProt

Q9NX02

n/a

RefSeq (mRNA)

NM_017852
NM_001174081
NM_001174082
NM_001174083
NM_001348003

NM_177690

RefSeq (protein)

NP_001167552
NP_001167553
NP_001167554
NP_060322
NP_001334932

n/a

Location (UCSC)Chr 19: 54.95 – 55 MbChr 7: 5.3 – 5.35 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

NACHT, LRR and PYD domains-containing protein 2 is a protein that in humans is encoded by the NLRP2 gene.[5][6][7]

NALP proteins, such as NALP2, are characterized by an N-terminal pyrin domain (PYD) and are involved in the activation of caspase-1 (CASP1; MIM 147678) by Toll-like receptors(see TLR4). They may also be involved in protein complexes that activate proinflammatory caspases (Tschopp et al., 2003).[supplied by OMIM][7][8]

Function

The NLRP2 gene is one of the family members of nucleotide-binding and leucine-rich repeat receptor (NLR). Information from many literature sources indicates that an N-terminal pyrin effector domain (PYD) is one of the components of the NLRP2 gene. Other components include a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR).[9] The products of NLRP2 gene are known to interact with IkB kinase (IKK) complex components. It can also regulate the activities of both caspase-1 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). The pyrin domain is essential and adequate to suppress the activities of NF-kB (Minkiewicz, de Rivero Vaccari and Keane 1113). An allelic variant (rs147585490) is known to block the NF-kB transcriptional activities. NLRP2 gene is one of the NLR family; it is believed to contribute to the regulation of immune responses (Minkiewicz, de Rivero Vaccari and Keane 1121). Although it is not well understood, the NLRP2 gene is responsible for maintaining fertility in females and contributes to the normal birth. The NPRP2 gene encodes for a human protein known as “NACHT, LRR and PYD domains-containing protein 2”.[10] NALP2, which is one of the NALP proteins, has an N-terminal pyrin characterization also encoded as MIM 608107 and PYD domain.[11] The NALP2 protein has a role in the activation process of caspase-1, which is encoded as CASP1; MIM 147678. The activation process occurs through the Toll-like receptors. The NALP2 may also take part in protein complexes, which initiates the activation of proinflammatory caspases.[12] NLR family regulates the functioning of the immune system, which technically compromises the normal functions of the body including reproduction.

Discovery

The NLR gene family where the NLRP2 gene belongs was first extracted from zebrafish, which is a common specimen for the study of immune systems. The NLRP2 gene is believed to have originated from the NLR gene family through mutation.[13] The mutation was initiated by the need for organisms to fit a dynamic environment and diversification in the evolution stages.[14] Also, the mutation of the NLR gene family proteins was also due to the ability of pathogens to subvert the defense mechanism of the host.[15] Therefore, the organisms were forced to device new ways of detecting and counteracting the effects of the resistant pathogens.[16] The evolution of the NLR proteins defines the origin of the NLRP2 gene. The NLRP2 gene is now an innate immune sensor for pathogens and sterile stress signal (SSS) in multi-cellular organisms.

Mutation and infertility

The deficiency of NLRP2 gene results in the inhibition of the activation of oocytes.[17] The NLRP2 gene is exclusively expressed in oocytes. Therefore, it regulates the quality of the oocytes, which explains its relation to infertility in females.[18]

References

  1. 1 2 3 ENSG00000275796, ENSG00000277060, ENSG00000275843, ENSG00000275399, ENSG00000022556, ENSG00000275082, ENSG00000278682, ENSG00000274638, ENSG00000273992 GRCh38: Ensembl release 89: ENSG00000278789, ENSG00000275796, ENSG00000277060, ENSG00000275843, ENSG00000275399, ENSG00000022556, ENSG00000275082, ENSG00000278682, ENSG00000274638, ENSG00000273992 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000035177 - 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 (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. ↑ Bertin J, DiStefano PS (December 2000). "The PYRIN domain: a novel motif found in apoptosis and inflammation proteins". Cell Death and Differentiation. 7 (12): 1273–4. doi:10.1038/sj.cdd.4400774. PMID 11270363.
  7. 1 2 "Entrez Gene: NLRP2 NLR family, pyrin domain containing 2".
  8. ↑ "NLRP2 NLR family pyrin domain containing 2 [ Homo sapiens (human) ]". NCBI.
  9. ↑ Minkiewicz J, de Rivero Vaccari JP, Keane RW (July 2013). "Human astrocytes express a novel NLRP2 inflammasome". Glia. 61 (7): 1113–21. doi:10.1002/glia.22499. PMID 23625868. S2CID 24606692.
  10. ↑ Acharya S, Saha S, Pradhan P (December 2018). "Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering". Gene. 679: 341–351. doi:10.1016/j.gene.2018.08.062. PMID 30184472. S2CID 52163882.
  11. ↑ Peng H, Liu H, Liu F, Gao Y, Chen J, Huo J, Han J, Xiao T, Zhang W (September 2017). "NLRP2 and FAF1 deficiency blocks early embryogenesis in the mouse". Reproduction. 154 (3): 245–251. doi:10.1530/REP-16-0629. PMID 28630100.
  12. ↑ Vizlin-Hodzic D, Zhai Q, Illes S, Södersten K, Truvé K, Parris TZ, et al. (January 2017). "Early onset of inflammation during ontogeny of bipolar disorder: the NLRP2 inflammasome gene distinctly differentiates between patients and healthy controls in the transition between iPS cell and neural stem cell stages". Translational Psychiatry. 7 (1): e1010. doi:10.1038/tp.2016.284. PMC 5545741. PMID 28117838.
  13. ↑ Acharya S, Saha S, Pradhan P (December 2018). "Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering". Gene. 679: 341–351. doi:10.1016/j.gene.2018.08.062. PMID 30184472. S2CID 52163882.
  14. ↑ Yang Y, Lang X, Sun S, Gao C, Hu J, Ding S, Li J, Li Y, Wang F, Gong T (November 2018). "NLRP2 negatively regulates antiviral immunity by interacting with TBK1". European Journal of Immunology. 48 (11): 1817–1825. doi:10.1002/eji.201847589. PMID 30183071.
  15. ↑ Minkiewicz J, de Rivero Vaccari JP, Keane RW (July 2013). "Human astrocytes express a novel NLRP2 inflammasome". Glia. 61 (7): 1113–21. doi:10.1002/glia.22499. PMID 23625868. S2CID 24606692.
  16. ↑ Mahadevan S, Sathappan V, Utama B, Lorenzo I, Kaskar K, Van den Veyver IB (April 2017). "Erratum: Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming". Scientific Reports. 7: 46434. Bibcode:2017NatSR...746434M. doi:10.1038/srep46434. PMC 5395947. PMID 28422141.
  17. ↑ Minkiewicz J, de Rivero Vaccari JP, Keane RW (July 2013). "Human astrocytes express a novel NLRP2 inflammasome". Glia. 61 (7): 1113–21. doi:10.1002/glia.22499. PMID 23625868. S2CID 24606692.
  18. ↑ Acharya S, Saha S, Pradhan P (December 2018). "Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering". Gene. 679: 341–351. doi:10.1016/j.gene.2018.08.062. PMID 30184472. S2CID 52163882.

Further reading

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