NLRP2
NACHT, LRR i protein 2 PYD sa domenom jest protein koji je kod ljudi kodiran genom NLRP2 sa hromosoma 19.[5][6][7]
Proteini NALP, kao što je NALP2, okarakterisani su N-terminalnim pirinskim domenom (PYD) i uključeni su u aktivaciju kaspaze-1 (CASP1; MIM 147678) receptorima sličnim Tollu (videti TLR4). Oni takođe mogu biti uključeni u proteinske komplekse koji aktiviraju proupalne kaspaze (Tschopp et al., 2003, prema OMIM].[7][8]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 1.062 aminokiseline, a molekulska težina 120.515 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MVSSAQMGFN | LQALLEQLSQ | DELSKFKYLI | TTFSLAHELQ | KIPHKEVDKA | ||||
| DGKQLVEILT | THCDSYWVEM | ASLQVFEKMH | RMDLSERAKD | EVREAALKSF | ||||
| NKRKPLSLGI | TRKERPPLDV | DEMLERFKTE | AQAFTETKGN | VICLGKEVFK | ||||
| GKKPDKDNRC | RYILKTKFRE | MWKSWPGDSK | EVQVMAERYK | MLIPFSNPRV | ||||
| LPGPFSYTVV | LYGPAGLGKT | TLAQKLMLDW | AEDNLIHKFK | YAFYLSCREL | ||||
| SRLGPCSFAE | LVFRDWPELQ | DDIPHILAQA | RKILFVIDGF | DELGAAPGAL | ||||
| IEDICGDWEK | KKPVPVLLGS | LLNRVMLPKA | ALLVTTRPRA | LRDLRILAEE | ||||
| PIYIRVEGFL | EEDRRAYFLR | HFGDEDQAMR | AFELMRSNAA | LFQLGSAPAV | ||||
| CWIVCTTLKL | QMEKGEDPVP | TCLTRTGLFL | RFLCSRFPQG | AQLRGALRTL | ||||
| SLLAAQGLWA | QTSVLHREDL | ERLGVQESDL | RLFLDGDILR | QDRVSKGCYS | ||||
| FIHLSFQQFL | TALFYTLEKE | EEEDRDGHTW | DIGDVQKLLS | GVERLRNPDL | ||||
| IQAGYYSFGL | ANEKRAKELE | ATFGCRMSPD | IKQELLRCDI | SCKGGHSTVT | ||||
| DLQELLGCLY | ESQEEELVKE | VMAQFKEISL | HLNAVDVVPS | SFCVKHCRNL | ||||
| QKMSLQVIKE | NLPENVTASE | SDAEVERSQD | DQHMLPFWTD | LCSIFGSNKD | ||||
| LMGLAINDSF | LSASLVRILC | EQIASDTCHL | QRVVFKNISP | ADAHRNLCLA | ||||
| LRGHKTVTYL | TLQGNDQDDM | FPALCEVLRH | PECNLRYLGL | VSCSATTQQW | ||||
| ADLSLALEVN | QSLTCVNLSD | NELLDEGAKL | LYTTLRHPKC | FLQRLSLENC | ||||
| HLTEANCKDL | AAVLVVSREL | THLCLAKNPI | GNTGVKFLCE | GLRYPECKLQ | ||||
| TLVLWNCDIT | SDGCCDLTKL | LQEKSSLLCL | DLGLNHIGVK | GMKFLCEALR | ||||
| KPLCNLRCLW | LWGCSIPPFS | CEDLCSALSC | NQSLVTLDLG | QNPLGSSGVK | ||||
| MLFETLTCSS | GTLRTLRLKI | DDFNDELNKL | LEEIEEKNPQ | LIIDTEKHHP | ||||
| WAERPSSHDF | MI |
Funkcija
urediNLRP2 gen je jedan od članova porodice receptora za ponavljanje koji se vezuju za nukleotide i leucin bogate receptore (NLR). Informacije iz mnogih izvora literature ukazuju da je N-terminalni pirin efektorski domen (PYD) jedna od komponenti gena NLRP2. Ostale komponente uključuju centralno lociran nukleotid-vezujući i oligomerizacijski domen (NACHT) i C-terminalnog poavljanja bogatog leucinom (LRR).[9] Poznato je da proizvodi gena NLRP2 komuniciraju sa komponentama kompleksa IkB kinaza (IKK). Također može da reguliše aktivnosti i kaspaze-1 i jedarnog faktora kapa-pojačivača lahkog lanca aktiviranih B-ćelija (NF-kB). Domen pirina je esencijalan i adekvatan za suzbijanje aktivnosti NF-kB (Minkiewicz, de Rivero Vaccari i Keane 1113). Poznato je da alelna varijanta (rs147585490) blokira aktivnosti transkripcije NF-kB. NLRP2 gen je jedan iz porodice NLR; vjeruje se da doprinosi regulaciji imunskih odgovora (Minkiewicz, de Rivero Vaccari i Keane 1121). Iako nije dobro shvaćen, gen NLRP2 odgovoran je za održavanje plodnosti kod ženki i doprinosi normalnom porođaju. NPRP2 gen kodira za ljudski protein poznat kao “NACHT, LRR i PYD domeni koji sadrže 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] NALP2 protein ima ulogu u procesu aktivacije kaspaze-1, koja je kodirana kao CASP1; MIM 147678. Proces aktivacije se odvija preko Toll-likog receptora. NALP2 također može učestvovati u proteinskim kompleksima, što pokreće aktivaciju proupalnih kaspaza.[12] NLR porodica reguliše funkcionisanje imunskog sistema, što tehnički ugrožava normalne funkcije tijela, uključujući reprodukciju.
Otkriće
urediPorodica NLR gena kojoj pripada gen NLRP2 prvo je ekstrahirana iz zebrica, uobičajenog model-organizma za proučavanje imunskog sistema. Vjeruje se da gen NLRP2 potiče iz porodice gena NLR putem mutacija.[13] The mutation was initiated by the need for organisms to fit a dynamic environment and diversification in the evolution stages.[14] Također, mutacija proteina iz porodice gena NLR bila je i posljedica sposobnosti patogena da potkopaju odbrambeni mehanizam domaćina..[9] Stoga su organizmi bili primorani da evoluiraju nove načine otkrivanja i suzbijanja efekata rezistentnih patogena.[15] Evolucija NLR proteina definira porijeklo NLRP2 gena. NLRP2 gen je sada urođeni imunski senzor za patogene i sterilni stresni signal (SSS) u višećelijskim organizmima.
Mutacija i neplodnost
urediNedostatak gena NLRP2 dovodi do inhibicije aktivacije oocita.[9] Gen NLRP2 je isključivo eksprimiran u oocitima. Stoga reguliše kvalitet oocita, što objašnjava njegovu vezu sa neplodnošću kod žena.[10]
Reference
uredi- ^ 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, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035177 - Ensembl, maj 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 (februar 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 (decembar 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 c "Entrez Gene: NLRP2 NLR family, pyrin domain containing 2".
- ^ "NLRP2 NLR family pyrin domain containing 2 [ Homo sapiens (human) ]". NCBI.
- ^ a b c Minkiewicz J, de Rivero Vaccari JP, Keane RW (juli 2013). "Human astrocytes express a novel NLRP2 inflammasome". Glia. 61 (7): 1113–21. doi:10.1002/glia.22499. PMID 23625868. S2CID 24606692.
- ^ a b Acharya S, Saha S, Pradhan P (decembar 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, Gao Y, Chen J, Huo J, Han J, Xiao T, Zhang W (septembar 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, Södersten K, Truvé K, Parris TZ, et al. (januar 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 (decembar 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, Gao C, Hu J, Ding S, Li J, Li Y, Wang F, Gong T (novembar 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.
- ^ 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.
Dopunska literatura
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- Maruyama K, Sugano S (januar 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, Suyama A, Sugano S (oktobar 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 (februar 2001). "The pyrin domain: a possible member of the death domain-fold family implicated in apoptosis and inflammation". Current Biology. 11 (4): R118-20. doi:10.1016/S0960-9822(01)00056-2. PMID 11250163. S2CID 18564343.
- Wang L, Manji GA, Grenier JM, Al-Garawi A, Merriam S, Lora JM, Geddes BJ, Briskin M, DiStefano PS, Bertin J (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.
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- Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J (mart 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, Chandler S, Stehlik C, Reed JC (decembar 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, Imamura R, Suda T (juni 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, Nieborowska-Skorska M, Urbanska K, Seferynska I, Reiss K, Skorski T (juli 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.