Search Results

Overview

Uniprot IDQ9C000
Protein NameNACHT, LRR and PYD domains-containing protein 1
Gene NameNLRP1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1428 TRPSQMRKLFSLSQS

Function

Acts as the sensor component of the NLRP1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:27662089, PubMed:31484767, PubMed:33093214, PubMed:33410748, PubMed:33731929, PubMed:33731932, PubMed:35857590). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:12191486, PubMed:17349957, PubMed:22665479). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as cleavage by some human enteroviruses and rhinoviruses, double-stranded RNA, UV-B irradiation, or Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex composed of NLRP1, CASP1 and PYCARD/ASC (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:25562666, PubMed:30096351, PubMed:30291141, PubMed:33093214, PubMed:33243852, PubMed:33410748, PubMed:35857590). In response to pathogen-associated signals, the N-terminal part of NLRP1 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and associates with PYCARD/ASC to initiate the formation of the inflammasome complex: the NLRP1 inflammasome recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:32051255, PubMed:33093214). In the absence of GSDMD expression, the NLRP1 inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME) (PubMed:33852854, PubMed:35594856). Activation of NLRP1 inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (PubMed:22801494). Binds ATP and shows ATPase activity (PubMed:11113115, PubMed:15212762, PubMed:33243852). Plays an important role in antiviral immunity and inflammation in the human airway epithelium (PubMed:33093214). Specifically recognizes a number of pathogen-associated signals: upon infection by human rhinoviruses 14 and 16 (HRV-14 and HRV-16), NLRP1 is cleaved and activated which triggers NLRP1-dependent inflammasome activation and IL18 secretion (PubMed:33093214). Positive-strand RNA viruses, such as Semliki forest virus and long dsRNA activate the NLRP1 inflammasome, triggering IL1B release in a NLRP1-dependent fashion (PubMed:33243852). Acts as a direct sensor for long dsRNA and thus RNA virus infection (PubMed:33243852). May also be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). The NLRP1 inflammasome is also activated in response to UV-B irradiation causing ribosome collisions: ribosome collisions cause phosphorylation and activation of NLRP1 in a MAP3K20-dependent manner, leading to pyroptosis (PubMed:35857590)

Protein Sequence

10 MAGGAWGRLA 20 CYLEFLKKEE 30 LKEFQLLLAN 40 KAHSRSSSGE 50 TPAQPEKTSG 60 MEVASYLVAQ 70 YGEQRAWDLA 80 LHTWEQMGLR 90 SLCAQAQEGA 100 GHSPSFPYSP 110 SEPHLGSPSQ 120 PTSTAVLMPW 130 IHELPAGCTQ 140 GSERRVLRQL 150 PDTSGRRWRE 160 ISASLLYQAL 170 PSSPDHESPS 180 QESPNAPTST 190 AVLGSWGSPP 200 QPSLAPREQE 210 APGTQWPLDE 220 TSGIYYTEIR 230 EREREKSEKG 240 RPPWAAVVGT 250 PPQAHTSLQP 260 HHHPWEPSVR 270 ESLCSTWPWK 280 NEDFNQKFTQ 290 LLLLQRPHPR 300 SQDPLVKRSW 310 PDYVEENRGH 320 LIEIRDLFGP 330 GLDTQEPRIV 340 ILQGAAGIGK 350 STLARQVKEA 360 WGRGQLYGDR 370 FQHVFYFSCR 380 ELAQSKVVSL 390 AELIGKDGTA 400 TPAPIRQILS 410 RPERLLFILD 420 GVDEPGWVLQ 430 EPSSELCLHW 440 SQPQPADALL 450 GSLLGKTILP 460 EASFLITART 470 TALQNLIPSL 480 EQARWVEVLG 490 FSESSRKEYF 500 YRYFTDERQA 510 IRAFRLVKSN 520 KELWALCLVP 530 WVSWLACTCL 540 MQQMKRKEKL 550 TLTSKTTTTL 560 CLHYLAQALQ 570 AQPLGPQLRD 580 LCSLAAEGIW 590 QKKTLFSPDD 600 LRKHGLDGAI 610 ISTFLKMGIL 620 QEHPIPLSYS 630 FIHLCFQEFF 640 AAMSYVLEDE 650 KGRGKHSNCI 660 IDLEKTLEAY 670 GIHGLFGAST 680 TRFLLGLLSD 690 EGEREMENIF 700 HCRLSQGRNL 710 MQWVPSLQLL 720 LQPHSLESLH 730 CLYETRNKTF 740 LTQVMAHFEE 750 MGMCVETDME 760 LLVCTFCIKF 770 SRHVKKLQLI 780 EGRQHRSTWS 790 PTMVVLFRWV 800 PVTDAYWQIL 810 FSVLKVTRNL 820 KELDLSGNSL 830 SHSAVKSLCK 840 TLRRPRCLLE 850 TLRLAGCGLT 860 AEDCKDLAFG 870 LRANQTLTEL 880 DLSFNVLTDA 890 GAKHLCQRLR 900 QPSCKLQRLQ 910 LVSCGLTSDC 920 CQDLASVLSA 930 SPSLKELDLQ 940 QNNLDDVGVR 950 LLCEGLRHPA 960 CKLIRLGLDQ 970 TTLSDEMRQE 980 LRALEQEKPQ 990 LLIFSRRKPS 1000 VMTPTEGLDT 1010 GEMSNSTSSL 1020 KRQRLGSERA 1030 ASHVAQANLK 1040 LLDVSKIFPI 1050 AEIAEESSPE 1060 VVPVELLCVP 1070 SPASQGDLHT 1080 KPLGTDDDFW 1090 GPTGPVATEV 1100 VDKEKNLYRV 1110 HFPVAGSYRW 1120 PNTGLCFVMR 1130 EAVTVEIEFC 1140 VWDQFLGEIN 1150 PQHSWMVAGP 1160 LLDIKAEPGA 1170 VEAVHLPHFV 1180 ALQGGHVDTS 1190 LFQMAHFKEE 1200 GMLLEKPARV 1210 ELHHIVLENP 1220 SFSPLGVLLK 1230 MIHNALRFIP 1240 VTSVVLLYHR 1250 VHPEEVTFHL 1260 YLIPSDCSIR 1270 KAIDDLEMKF 1280 QFVRIHKPPP 1290 LTPLYMGCRY 1300 TVSGSGSGML 1310 EILPKELELC 1320 YRSPGEDQLF 1330 SEFYVGHLGS 1340 GIRLQVKDKK 1350 DETLVWEALV 1360 KPGDLMPATT 1370 LIPPARIAVP 1380 SPLDAPQLLH 1390 FVDQYREQLI 1400 ARVTSVEVVL 1410 DKLHGQVLSQ 1420 EQYERVLAEN 1430 TRPSQMRKLF 1440 SLSQSWDRKC 1450 KDGLYQALKE 1460 THPHLIMELW 1470 EKGSKKGLLP LSS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0072558 NLRP1 inflammasome complex
Cellular Component GO:0072559 NLRP3 inflammasome complex
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0140608 cysteine-type endopeptidase activator activity
Molecular Function GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process
Molecular Function GO:0003690 double-stranded DNA binding
Molecular Function GO:0003725 double-stranded RNA binding
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0140693 molecular condensate scaffold activity
Molecular Function GO:0038187 pattern recognition receptor activity
Molecular Function GO:0008233 peptidase activity
Molecular Function GO:0019904 protein domain specific binding
Molecular Function GO:0035591 signaling adaptor activity
Biological Process GO:0002218 activation of innate immune response
Biological Process GO:0140374 antiviral innate immune response
Biological Process GO:0006915 apoptotic process
Biological Process GO:0071493 cellular response to UV-B
Biological Process GO:0042742 defense response to bacterium
Biological Process GO:0051607 defense response to virus
Biological Process GO:0006954 inflammatory response
Biological Process GO:0097193 intrinsic apoptotic signaling pathway
Biological Process GO:0051402 neuron apoptotic process
Biological Process GO:1904784 NLRP1 inflammasome complex assembly
Biological Process GO:0002221 pattern recognition receptor signaling pathway
Biological Process GO:0050729 positive regulation of inflammatory response
Biological Process GO:0032731 positive regulation of interleukin-1 beta production
Biological Process GO:0051260 protein homooligomerization
Biological Process GO:0070269 pyroptotic inflammatory response
Biological Process GO:0042981 regulation of apoptotic process
Biological Process GO:0050727 regulation of inflammatory response
Biological Process GO:0032495 response to muramyl dipeptide
Biological Process GO:0097264 self proteolysis
Biological Process GO:0007165 signal transduction

Reference

[1] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.