NLRP2

Protein-coding gene in the species Homo sapiens

NLRP2

Identifiers

Aliases

NLRP2, CLR19.9, NALP2, NBS1, PAN1, PYPAF2, NLR family, pyrin domain containing 2, NLR family pyrin domain containing 2

External IDs

OMIM: 609364 MGI: 3041206 HomoloGene: 56789 GeneCards: NLRP2

Gene location (Human)

Chr.	Chromosome 19 (human)^[1]

Band	19q13.42	Start	54,953,130 bp^[1]
Band	19q13.42	End	55,001,142 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 7 (mouse)^[2]

Band	7\|7 A1	Start	5,301,546 bp^[2]
Band	7\|7 A1	End	5,354,034 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

placenta

testicle

ganglionic eminence

lymph node

blood

endometrium

islet of Langerhans

thymus

appendix

spleen

Top expressed in

secondary oocyte

morula

ovarian follicle

blastocyst

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	Pyrin domain binding nucleotide binding protein binding ATP binding
Cellular component	cytoplasm Golgi apparatus intracellular membrane-bounded organelle cytosol
Biological process	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process inflammatory response innate immune response immune system process apoptotic process negative regulation of NF-kappaB transcription factor activity
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


55655


232827

Ensembl

ENSG00000278789 ENSG00000275796 ENSG00000277060 ENSG00000275843 ENSG00000275399
ENSG00000022556 ENSG00000275082 ENSG00000278682 ENSG00000274638 ENSG00000273992


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 Mb

Chr 7: 5.3 – 5.35 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/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

^ ^a ^b ^c 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
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000035177 – 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.
^ 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.
^ 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.
^ ^a ^b "Entrez Gene: NLRP2 NLR family, pyrin domain containing 2".
^ "NLRP2 NLR family pyrin domain containing 2 [ Homo sapiens (human) ]". NCBI.
^ 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.
^ 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.
^ Peng H, Liu H, Liu F, et al. (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.
^ Vizlin-Hodzic D, Zhai Q, Illes S, 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.
^ 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.
^ Yang Y, Lang X, Sun S, et al. (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.
^ 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.
^ Mahadevan S, Sathappan V, Utama B, et al. (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.
^ 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.
^ 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.

Teng SC, Wu KJ, Tseng SF, et al. (September 2006). "Importin KPNA2, NBS1, DNA repair and tumorigenesis". Journal of Molecular Histology. 37 (5–7): 293–9. doi:10.1007/s10735-006-9032-y. PMID 16752129. S2CID 7281949.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Martinon F, Hofmann K, Tschopp J (February 2001). "The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation". Current Biology. 11 (4): R118-20. Bibcode:2001CBio...11.R118M. doi:10.1016/S0960-9822(01)00056-2. PMID 11250163. S2CID 18564343.
Wang L, Manji GA, Grenier JM, et al. (August 2002). "PYPAF7, a novel PYRIN-containing Apaf1-like protein that regulates activation of NF-kappa B and caspase-1-dependent cytokine processing". The Journal of Biological Chemistry. 277 (33): 29874–80. doi:10.1074/jbc.M203915200. PMID 12019269.
Grenier JM, Wang L, Manji GA, et al. (October 2002). "Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1". FEBS Letters. 530 (1–3): 73–8. doi:10.1016/S0014-5793(02)03416-6. PMID 12387869. S2CID 25023390.
Agostini L, Martinon F, Burns K, et al. (March 2004). "NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder". Immunity. 20 (3): 319–25. doi:10.1016/S1074-7613(04)00046-9. PMID 15030775.
Bruey JM, Bruey-Sedano N, Newman R, et al. (December 2004). "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages". The Journal of Biological Chemistry. 279 (50): 51897–907. doi:10.1074/jbc.M406741200. PMID 15456791.
Kinoshita T, Wang Y, Hasegawa M, et al. (June 2005). "PYPAF3, a PYRIN-containing APAF-1-like protein, is a feedback regulator of caspase-1-dependent interleukin-1beta secretion". The Journal of Biological Chemistry. 280 (23): 21720–5. doi:10.1074/jbc.M410057200. PMID 15817483.
Rink L, Slupianek A, Stoklosa T, et al. (July 2007). "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". Blood. 110 (2): 651–60. doi:10.1182/blood-2006-08-042630. PMC 1924483. PMID 17431132.