NLRP2
{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{technical|date=November 2018}}
{{Infobox_gene}}
NACHT, LRR and PYD domains-containing protein 2 is a protein that in humans is encoded by the NLRP2 gene.{{cite journal | vauthors = Tschopp J, Martinon F, Burns K | title = NALPs: a novel protein family involved in inflammation | journal = Nature Reviews. Molecular Cell Biology | volume = 4 | issue = 2 | pages = 95–104 | date = February 2003 | pmid = 12563287 | doi = 10.1038/nrm1019 | s2cid = 31417018 }}{{cite journal | vauthors = Bertin J, DiStefano PS | title = The PYRIN domain: a novel motif found in apoptosis and inflammation proteins | journal = Cell Death and Differentiation | volume = 7 | issue = 12 | pages = 1273–4 | date = December 2000 | pmid = 11270363 | doi = 10.1038/sj.cdd.4400774 | doi-access = free }}
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]{{cite web | title = Entrez Gene: NLRP2 NLR family, pyrin domain containing 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55655}}{{cite web |title=NLRP2 NLR family pyrin domain containing 2 [ Homo sapiens (human) ] |url=https://www.ncbi.nlm.nih.gov/gene/55655 |website=NCBI}}
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).{{cite journal | vauthors = Minkiewicz J, de Rivero Vaccari JP, Keane RW | title = Human astrocytes express a novel NLRP2 inflammasome | journal = Glia | volume = 61 | issue = 7 | pages = 1113–21 | date = July 2013 | pmid = 23625868 | doi = 10.1002/glia.22499 | s2cid = 24606692 }} 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".{{cite journal | vauthors = Acharya S, Saha S, Pradhan P | title = Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering | journal = Gene | volume = 679 | pages = 341–351 | date = December 2018 | pmid = 30184472 | doi = 10.1016/j.gene.2018.08.062 | s2cid = 52163882 }} NALP2, which is one of the NALP proteins, has an N-terminal pyrin characterization also encoded as MIM 608107 and PYD domain.{{cite journal | vauthors = Peng H, Liu H, Liu F, Gao Y, Chen J, Huo J, Han J, Xiao T, Zhang W | title = NLRP2 and FAF1 deficiency blocks early embryogenesis in the mouse | journal = Reproduction | volume = 154 | issue = 3 | pages = 245–251 | date = September 2017 | pmid = 28630100 | doi = 10.1530/REP-16-0629 }} 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.{{cite journal | vauthors = Vizlin-Hodzic D, Zhai Q, Illes S, Södersten K, Truvé K, Parris TZ, Sobhan PK, Salmela S, Kosalai ST, Kanduri C, Strandberg J, Seth H, Bontell TO, Hanse E, Ågren H, Funa K | title = 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 | journal = Translational Psychiatry | volume = 7 | issue = 1 | pages = e1010 | date = January 2017 | pmid = 28117838 | pmc = 5545741 | doi = 10.1038/tp.2016.284 }} 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.{{cite journal | vauthors = Acharya S, Saha S, Pradhan P | title = Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering | journal = Gene | volume = 679 | pages = 341–351 | date = December 2018 | pmid = 30184472 | doi = 10.1016/j.gene.2018.08.062 | s2cid = 52163882 | url = https://www.researchgate.net/publication/327387339 }} The mutation was initiated by the need for organisms to fit a dynamic environment and diversification in the evolution stages.{{cite journal | vauthors = Yang Y, Lang X, Sun S, Gao C, Hu J, Ding S, Li J, Li Y, Wang F, Gong T | title = NLRP2 negatively regulates antiviral immunity by interacting with TBK1 | journal = European Journal of Immunology | volume = 48 | issue = 11 | pages = 1817–1825 | date = November 2018 | pmid = 30183071 | doi = 10.1002/eji.201847589 | doi-access = free }} 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.{{cite journal | vauthors = Minkiewicz J, de Rivero Vaccari JP, Keane RW | title = Human astrocytes express a novel NLRP2 inflammasome | journal = Glia | volume = 61 | issue = 7 | pages = 1113–21 | date = July 2013 | pmid = 23625868 | doi = 10.1002/glia.22499 | s2cid = 24606692 }} Therefore, the organisms were forced to device new ways of detecting and counteracting the effects of the resistant pathogens.{{cite journal | vauthors = Mahadevan S, Sathappan V, Utama B, Lorenzo I, Kaskar K, Van den Veyver IB | title = Erratum: Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming | journal = Scientific Reports | volume = 7 | pages = 46434 | date = April 2017 | pmid = 28422141 | pmc = 5395947 | doi = 10.1038/srep46434 | bibcode = 2017NatSR...746434M }} 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.{{cite journal | vauthors = Minkiewicz J, de Rivero Vaccari JP, Keane RW | title = Human astrocytes express a novel NLRP2 inflammasome | journal = Glia | volume = 61 | issue = 7 | pages = 1113–21 | date = July 2013 | pmid = 23625868 | doi = 10.1002/glia.22499 | s2cid = 24606692 }} The NLRP2 gene is exclusively expressed in oocytes. Therefore, it regulates the quality of the oocytes, which explains its relation to infertility in females.{{cite journal | vauthors = Acharya S, Saha S, Pradhan P | title = Novel symmetry-based gene-gene dissimilarity measures utilizing Gene Ontology: Application in gene clustering | journal = Gene | volume = 679 | pages = 341–351 | date = December 2018 | pmid = 30184472 | doi = 10.1016/j.gene.2018.08.062 | s2cid = 52163882 }}{{clear}}
References
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Further reading
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- {{cite journal | vauthors = Teng SC, Wu KJ, Tseng SF, Wong CW, Kao L | title = Importin KPNA2, NBS1, DNA repair and tumorigenesis | journal = Journal of Molecular Histology | volume = 37 | issue = 5–7 | pages = 293–9 | date = September 2006 | pmid = 16752129 | doi = 10.1007/s10735-006-9032-y | s2cid = 7281949 }}
- {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
- {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
- {{cite journal | vauthors = Martinon F, Hofmann K, Tschopp J | title = The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation | journal = Current Biology | volume = 11 | issue = 4 | pages = R118-20 | date = February 2001 | pmid = 11250163 | doi = 10.1016/S0960-9822(01)00056-2 | s2cid = 18564343 | doi-access = free | bibcode = 2001CBio...11.R118M }}
- {{cite journal | vauthors = Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J | title = PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing | journal = The Journal of Biological Chemistry | volume = 277 | issue = 33 | pages = 29874–80 | date = August 2002 | pmid = 12019269 | doi = 10.1074/jbc.M203915200 | doi-access = free }}
- {{cite journal | vauthors = Grenier JM, Wang L, Manji GA, Huang WJ, Al-Garawi A, Kelly R, Carlson A, Merriam S, Lora JM, Briskin M, DiStefano PS, Bertin J | title = Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1 | journal = FEBS Letters | volume = 530 | issue = 1–3 | pages = 73–8 | date = October 2002 | pmid = 12387869 | doi = 10.1016/S0014-5793(02)03416-6 | s2cid = 25023390 }}
- {{cite journal | vauthors = Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J | title = NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder | journal = Immunity | volume = 20 | issue = 3 | pages = 319–25 | date = March 2004 | pmid = 15030775 | doi = 10.1016/S1074-7613(04)00046-9 | doi-access = free }}
- {{cite journal | vauthors = Bruey JM, Bruey-Sedano N, Newman R, Chandler S, Stehlik C, Reed JC | title = PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages | journal = The Journal of Biological Chemistry | volume = 279 | issue = 50 | pages = 51897–907 | date = December 2004 | pmid = 15456791 | doi = 10.1074/jbc.M406741200 | doi-access = free }}
- {{cite journal | vauthors = Kinoshita T, Wang Y, Hasegawa M, Imamura R, Suda T | title = PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta secretion | journal = The Journal of Biological Chemistry | volume = 280 | issue = 23 | pages = 21720–5 | date = June 2005 | pmid = 15817483 | doi = 10.1074/jbc.M410057200 | doi-access = free | hdl = 2297/2649 | hdl-access = free }}
- {{cite journal | vauthors = Rink L, Slupianek A, Stoklosa T, Nieborowska-Skorska M, Urbanska K, Seferynska I, Reiss K, Skorski T | title = Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11-RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against BCR/ABL-positive leukemia cells | journal = Blood | volume = 110 | issue = 2 | pages = 651–60 | date = July 2007 | pmid = 17431132 | pmc = 1924483 | doi = 10.1182/blood-2006-08-042630 }}
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{{NOD-like receptors}}
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