NLRP1
entrez
22861
canonical
uniprot
Q9C000
canonical
ensembl
ENSG00000091592
resolver
ensp
ENSP00000262467
resolver
ensp
ENSP00000346390
resolver
ensp
ENSP00000459661
resolver
ensp
ENSP00000460216
resolver
ensp
ENSP00000460475
resolver
genesymbol
NLRP1
resolver
genesymbol_syn
CARD7
resolver
genesymbol_syn
DEFCAP
resolver
genesymbol_syn
KIAA0926
resolver
genesymbol_syn
NAC
resolver
genesymbol_syn
NALP1
resolver
hgnc
HGNC:14374
resolver
uniprot
E9PE50
resolver
uniprot
I6L9D9
resolver
uniprot
Q9BZZ8
resolver
uniprot
Q9BZZ9
resolver
uniprot
Q9H5Z7
resolver
uniprot
Q9H5Z8
resolver
uniprot
Q9HAV8
resolver
uniprot
Q9UFT4
resolver
uniprot
Q9Y2E0
resolver
uniprot_entry
NLRP1_HUMAN
resolver
uniprot_sec
E9PE50
resolver
uniprot_sec
I6L9D9
resolver
uniprot_sec
Q9BZZ8
resolver
uniprot_sec
Q9BZZ9
resolver
uniprot_sec
Q9H5Z7
resolver
uniprot_sec
Q9H5Z8
resolver
uniprot_sec
Q9HAV8
resolver
uniprot_sec
Q9UFT4
resolver
uniprot_sec
Q9Y2E0
resolver
activity_regulation
ACTIVITY REGULATION: NLRP1 inflammasome is activated by cleavage by the Protease 3C from various human enteroviruses and rhinoviruses (EV68, EV71, Coxsackievirus B3, HRV-14 and HRV-16): cleavage promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the NLRP1 inflammasome (PubMed:33093214, PubMed:33410748). Activated double-stranded RNA: positive-strand RNA viruses such as Semliki forest virus and long dsRNA activate the NLRP1 inflammasome (PubMed:33243852). In contrast to its mouse ortholog, not activated by Bacillus anthracis lethal toxin (PubMed:19651869). NLRP1 inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) in a ternary complex, thereby preventing NLRP1 oligomerization and activation (PubMed:30291141, PubMed:31525884, PubMed:33731929, PubMed:33731932). NLRP1 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:30291141, PubMed:33731929, PubMed:33731932). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (PubMed:33731929, PubMed:33731932). ATPase activity is activated by dsRNA-binding but not dsDNA-binding (PubMed:33243852). {ECO:0000269|PubMed:19651869, ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:31525884, ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33243852, ECO:0000269|PubMed:33410748, ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932}.; ACTIVITY REGULATION: (Microbial infection) The NLRP1 inflammasome is activated by human herpes virus 8/HHV-8 protein ORF45, which interacts with the N-terminal part of NLRP1 and promotes its translocation into the nucleus, relieving autoinhibition and leading to activation. {ECO:0000269|PubMed:35618833}.; ACTIVITY REGULATION: (Microbial infection) NLRP1 inflammasome is activated by cleavage by the 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2. {ECO:0000269|PubMed:35594856}.
uniprot
proteins
amino_acid_sequence
MAGGAWGRLACYLEFLKKEELKEFQLLLANKAHSRSSSGETPAQPEKTSGMEVASYLVAQYGEQRAWDLALHTWEQMGLRSLCAQAQEGAGHSPSFPYSPSEPHLGSPSQPTSTAVLMPWIHELPAGCTQGSERRVLRQLPDTSGRRWREISASLLYQALPSSPDHESPSQESPNAPTSTAVLGSWGSPPQPSLAPREQEAPGTQWPLDETSGIYYTEIREREREKSEKGRPPWAAVVGTPPQAHTSLQPHHHPWEPSVRESLCSTWPWKNEDFNQKFTQLLLLQRPHPRSQDPLVKRSWPDYVEENRGHLIEIRDLFGPGLDTQEPRIVILQGAAGIGKSTLARQVKEAWGRGQLYGDRFQHVFYFSCRELAQSKVVSLAELIGKDGTATPAPIRQILSRPERLLFILDGVDEPGWVLQEPSSELCLHWSQPQPADALLGSLLGKTILPEASFLITARTTALQNLIPSLEQARWVEVLGFSESSRKEYFYRYFTDERQAIRAFRLVKSNKELWALCLVPWVSWLACTCLMQQMKRKEKLTLTSKTTTTLCLHYLAQALQAQPLGPQLRDLCSLAAEGIWQKKTLFSPDDLRKHGLDGAIISTFLKMGILQEHPIPLSYSFIHLCFQEFFAAMSYVLEDEKGRGKHSNCIIDLEKTLEAYGIHGLFGASTTRFLLGLLSDEGEREMENIFHCRLSQGRNLMQWVPSLQLLLQPHSLESLHCLYETRNKTFLTQVMAHFEEMGMCVETDMELLVCTFCIKFSRHVKKLQLIEGRQHRSTWSPTMVVLFRWVPVTDAYWQILFSVLKVTRNLKELDLSGNSLSHSAVKSLCKTLRRPRCLLETLRLAGCGLTAEDCKDLAFGLRANQTLTELDLSFNVLTDAGAKHLCQRLRQPSCKLQRLQLVSCGLTSDCCQDLASVLSASPSLKELDLQQNNLDDVGVRLLCEGLRHPACKLIRLGLDQTTLSDEMRQELRALEQEKPQLLIFSRRKPSVMTPTEGLDTGEMSNSTSSLKRQRLGSERAASHVAQANLKLLDVSKIFPIAEIAEESSPEVVPVELLCVPSPASQGDLHTKPLGTDDDFWGPTGPVATEVVDKEKNLYRVHFPVAGSYRWPNTGLCFVMREAVTVEIEFCVWDQFLGEINPQHSWMVAGPLLDIKAEPGAVEAVHLPHFVALQGGHVDTSLFQMAHFKEEGMLLEKPARVELHHIVLENPSFSPLGVLLKMIHNALRFIPVTSVVLLYHRVHPEEVTFHLYLIPSDCSIRKAIDDLEMKFQFVRIHKPPPLTPLYMGCRYTVSGSGSGMLEILPKELELCYRSPGEDQLFSEFYVGHLGSGIRLQVKDKKDETLVWEALVKPGDLMPATTLIPPARIAVPSPLDAPQLLHFVDQYREQLIARVTSVEVVLDKLHGQVLSQEQYERVLAENTRPSQMRKLFSLSQSWDRKCKDGLYQALKETHPHLIMELWEKGSKKGLLPLSS
uniprot
proteins
disease_involvement
DISEASE: Vitiligo-associated multiple autoimmune disease 1 (VAMAS1) [MIM:606579]: A disorder characterized by the association of vitiligo with several autoimmune and autoinflammatory diseases including autoimmune thyroid disease, rheumatoid arthritis and systemic lupus erythematosus. {ECO:0000269|PubMed:17377159}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Palmoplantar carcinoma, multiple self-healing (MSPC) [MIM:615225]: An autosomal dominant disease characterized by keratopathy with neovascularization, bilateral corneal opacification, palmoplantar hyperkeratosis, dyshidrosis, dystrophic nails, and recurrent keratoacanthomas in palmoplantar skin as well as in conjunctival and corneal epithelia. In addition, patients experience a high susceptibility to malignant squamous cell carcinoma. {ECO:0000269|PubMed:23349227, ECO:0000269|PubMed:27662089, ECO:0000269|PubMed:33093214}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Autoinflammation with arthritis and dyskeratosis (AIADK) [MIM:617388]: A disorder characterized by recurrent fever, diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Inheritance can be autosomal dominant or autosomal recessive. {ECO:0000269|PubMed:27965258, ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:33731932}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Respiratory papillomatosis, juvenile recurrent, congenital (JRRP) [MIM:618803]: An autosomal recessive disease characterized by recurrent growth of papillomas in the respiratory tract, and onset in early childhood. Papillomas are most commonly found in the larynx but may occur anywhere from the mouth to the bronchi. Children typically present within the first years of life with hoarseness or, in more severe cases, respiratory distress or stridor and airway obstruction. JRRP is associated with infection of the upper airway by human papillomaviruses of the alpha genus. The infection is thought to occur by vertical transmission at birth. {ECO:0000269|PubMed:31484767}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.-.-
uniprot
proteins
ec_number
3.6.4.-
uniprot
proteins
function
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). {ECO:0000269|PubMed:11113115, ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:15212762, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:25562666, ECO:0000269|PubMed:27662089, ECO:0000269|PubMed:30096351, ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:31484767, ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33243852, ECO:0000269|PubMed:33410748, ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932, ECO:0000269|PubMed:33852854, ECO:0000269|PubMed:35594856, ECO:0000269|PubMed:35857590}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1]: Constitutes the precursor of the NLRP1 inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals. {ECO:0000269|PubMed:22087307}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: Regulatory part that prevents formation of the NLRP1 inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus), preventing activation of the NLRP1 inflammasome (PubMed:33093214). In response to pathogen-associated signals, this part is ubiquitinated and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the NLRP1 inflammasome (PubMed:33093214). {ECO:0000269|PubMed:33093214}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]: Constitutes the active part of the NLRP1 inflammasome (PubMed:33093214, PubMed:33731929, PubMed:33731932). In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, N-terminus), preventing activation of the NLRP1 inflammasome (PubMed:33093214). In response to pathogen-associated signals, the N-terminal part of NLRP1 is degraded by the proteasome, releasing this form, which polymerizes and associates with PYCARD/ASC to form of the NLRP1 inflammasome complex: the NLRP1 inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis (PubMed:33093214). {ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33731929, ECO:0000269|PubMed:33731932}.; FUNCTION: [Isoform 2]: It is unclear whether is involved in inflammasome formation. It is not cleaved within the FIIND domain, does not assemble into specks, nor promote IL1B release (PubMed:22665479). However, in an vitro cell-free system, it has been shown to be activated by MDP (PubMed:17349957). {ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:22665479}.
uniprot
proteins
mass_dalton
165866
uniprot
proteins
mutagenesis
MUTAGEN 76; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 85; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 87; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 110; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 130; /note="Q->A: Inhibits cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 130; /note="Q->P: Inhibits cleavage by Protease 3C from Coxsackievirus B3 and HRV-14."; /evidence="ECO:0000269|PubMed:33410748"; MUTAGEN 139; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 158; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 171; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 178..180; /note="TST->AAA: In 3A mutant; abolished activation of the NLRP1 inflammasome in response to UV-B irradiation and ribosome collisions."; /evidence="ECO:0000269|PubMed:35857590"; MUTAGEN 191; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 199; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 205; /note="Q->A: No effect on cleavage by HRV-14 Protease 3C."; /evidence="ECO:0000269|PubMed:33093214"; MUTAGEN 333; /note="Q->A: Abolished cleavage by the 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2."; /evidence="ECO:0000269|PubMed:35594856"; MUTAGEN 339..340; /note="GK->EA: Loss of ATP binding."; /evidence="ECO:0000269|PubMed:15212762"; MUTAGEN 340; /note="K->L,S: No effect."; /evidence="ECO:0000269|PubMed:11076957"; MUTAGEN 1168; /note="H->A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine."; /evidence="ECO:0000269|PubMed:22665479"; MUTAGEN 1186; /note="H->A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing can be restored by treatment with hydroxylamine."; /evidence="ECO:0000269|PubMed:22665479"; MUTAGEN 1193..1194; /note="LL->EE: Reduced autocatalytic processing and reduced interaction with DPP9."; /evidence="ECO:0000269|PubMed:33731932"; MUTAGEN 1211; /note="S->A: Partial loss of autocatalytic processing and of IL1B release."; /evidence="ECO:0000269|PubMed:22665479"; MUTAGEN 1212; /note="F->A: Complete loss of autocatalytic processing and of IL1B release."; /evidence="ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:33093214"; MUTAGEN 1213; /note="S->A: Complete loss of autocatalytic processing and of IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine. Abolished interaction with DPP9. Loss of activation by dsRNA or positive-strand RNA virus."; /evidence="ECO:0000269|PubMed:22087307, ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:31525884, ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:33243852, ECO:0000269|PubMed:33731932"; MUTAGEN 1213; /note="S->C: Complete loss of autocatalytic processing, which can be restored by treatment with hydroxylamine."; /evidence="ECO:0000269|PubMed:22665479"; MUTAGEN 1214; /note="P->A: Partial loss of autocatalytic processing (50%) and of IL1B release (50%)."; /evidence="ECO:0000269|PubMed:22665479"; MUTAGEN 1240; /note="R->D: Slightly reduced formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1249; /note="H->A: Complete loss of autocatalytic processing and IL1B release. Autocatalytic processing cannot be restored by treatment with hydroxylamine."; /evidence="ECO:0000269|PubMed:22665479"; MUTAGEN 1260..1261; /note="RK->DD: Slightly reduced formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1276; /note="H->G: Abolished ability to form the NLRP1 inflammasome."; /evidence="ECO:0000269|PubMed:33731932"; MUTAGEN 1277; /note="K->E: Abolished ability to form the NLRP1 inflammasome."; /evidence="ECO:0000269|PubMed:33731932"; MUTAGEN 1278..1279; /note="PP->AG: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1278; /note="P->E: Impaired ability to form the NLRP1 inflammasome."; /evidence="ECO:0000269|PubMed:33731929"; MUTAGEN 1281; /note="L->E: Impaired ability to form the NLRP1 inflammasome."; /evidence="ECO:0000269|PubMed:33731929"; MUTAGEN 1320; /note="F->A: Slightly reduced formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1322; /note="E->R: Abolished ability to form the NLRP1 inflammasome."; /evidence="ECO:0000269|PubMed:33731932"; MUTAGEN 1383; /note="D->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1386; /note="R->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1387; /note="E->R: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1388; /note="Q->D: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1392; /note="R->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1392; /note="R->E: Impaired ability to induce programmed cell death."; /evidence="ECO:0000269|PubMed:33420033"; MUTAGEN 1395; /note="S->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1397; /note="E->R: Impaired ability to induce programmed cell death. Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033"; MUTAGEN 1401; /note="D->R: Impaired ability to induce programmed cell death."; /evidence="ECO:0000269|PubMed:33420033"; MUTAGEN 1402; /note="K->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1402; /note="K->E: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1404; /note="H->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1406; /note="Q->R: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1410; /note="Q->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1411; /note="E->R: Impaired ability to induce programmed cell death. Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033"; MUTAGEN 1413; /note="Y->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1414; /note="E->R: Impaired ability to induce programmed cell death. Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033"; MUTAGEN 1415; /note="R->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1420; /note="N->E: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1422; /note="R->E: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1427; /note="R->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1427; /note="R->E: Impaired ability to induce programmed cell death."; /evidence="ECO:0000269|PubMed:33420033"; MUTAGEN 1428; /note="K->E: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1434; /note="Q->R: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1437; /note="D->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1445; /note="Y->A: Abolished inflammasome filament formation. Impaired ability to induce programmed cell death, but retains CAPS1 processing."; /evidence="ECO:0000269|PubMed:33420033"; MUTAGEN 1449; /note="K->D: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1450; /note="E->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1451; /note="T->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1454; /note="H->D: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1454; /note="H->E: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1457; /note="M->A: Does not affect ability to induce programmed cell death."; /evidence="ECO:0000269|PubMed:33420033"; MUTAGEN 1458; /note="E->R: Abolished formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028"; MUTAGEN 1460; /note="W->A: Does not affect ability to induce programmed cell death."; /evidence="ECO:0000269|PubMed:33420033"; MUTAGEN 1461; /note="E->R: Does not affect formation of an inflammasome filament together with PYCARD/ASC."; /evidence="ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033
uniprot
proteins
post_translational_modification
PTM: [NACHT, LRR and PYD domains-containing protein 1]: Autocatalytically cleaved (PubMed:22087307, PubMed:22665479, PubMed:33093214). Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding (PubMed:22087307, PubMed:22665479, PubMed:33093214). Both N- and C-terminal parts remain associated non-covalently (PubMed:22087307, PubMed:22665479, PubMed:33093214). {ECO:0000269|PubMed:22087307, ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:33093214}.; PTM: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: Ubiquitinated by the cullin:ZER1/ZYG11B complex in response to pathogen-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and forms the NLRP1 inflammasome. {ECO:0000269|PubMed:33093214}.; PTM: Phosphorylated by MAP3K20 isoform ZAKalpha, MAPK11 and MAPK14 in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis. {ECO:0000269|PubMed:35857590}.; PTM: (Microbial infection) Cleaved between Gln-130 and Gly-131 by the Protease 3C from various human enteroviruses and rhinoviruses (EV68, EV71, Coxsackievirus B3, HRV-14 and HRV-16) (PubMed:33093214, PubMed:33410748). This cleavage triggers N-glycine-mediated proteasomal degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullin:ZER1/ZYG11B complex which liberates the activating C-terminal fragment and activates NLRP1 inflammasome (PubMed:33093214). {ECO:0000269|PubMed:33093214, ECO:0000269|PubMed:33410748}.; PTM: (Microbial infection) Cleaved between Gln-333 and Gly-334 by the 3C-like proteinase nsp5 from human coronavirus SARS-CoV-2 (PubMed:35594856). This cleavage liberates the activating C-terminal fragment and activates NLRP1 inflammasome, leading to downstream activation of GSDME and lung epithelial cell death (PubMed:35594856). {ECO:0000269|PubMed:35594856}.
uniprot
proteins
protein_family
NLRP family
uniprot
proteins
pubmed
10231032
uniprot
proteins
pubmed
11076957
uniprot
proteins
pubmed
11113115
uniprot
proteins
pubmed
11250163
uniprot
proteins
pubmed
11270363
uniprot
proteins
pubmed
12191486
uniprot
proteins
pubmed
14527388
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15212762
uniprot
proteins
pubmed
15285719
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16439990
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17164409
uniprot
proteins
pubmed
17349957
uniprot
proteins
pubmed
17377159
uniprot
proteins
pubmed
17418785
uniprot
proteins
pubmed
17431422
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18511561
uniprot
proteins
pubmed
19651869
uniprot
proteins
pubmed
22087307
uniprot
proteins
pubmed
22665479
uniprot
proteins
pubmed
22801494
uniprot
proteins
pubmed
23349227
uniprot
proteins
pubmed
24439873
uniprot
proteins
pubmed
25562666
uniprot
proteins
pubmed
26086088
uniprot
proteins
pubmed
26347139
uniprot
proteins
pubmed
27662089
uniprot
proteins
pubmed
27965258
uniprot
proteins
pubmed
30096351
uniprot
proteins
pubmed
30291141
uniprot
proteins
pubmed
31484767
uniprot
proteins
pubmed
31525884
uniprot
proteins
pubmed
32051255
uniprot
proteins
pubmed
32558991
uniprot
proteins
pubmed
33093214
uniprot
proteins
pubmed
33243852
uniprot
proteins
pubmed
33410748
uniprot
proteins
pubmed
33420028
uniprot
proteins
pubmed
33420033
uniprot
proteins
pubmed
33731929
uniprot
proteins
pubmed
33731932
uniprot
proteins
pubmed
33852854
uniprot
proteins
pubmed
35594856
uniprot
proteins
pubmed
35618833
uniprot
proteins
pubmed
35857590
uniprot
proteins
sequence_length
1473
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17418785}. Cytoplasm {ECO:0000269|PubMed:17164409}. Nucleus {ECO:0000269|PubMed:17164409}. Note=Nucleocytoplasmic distribution in lymphoid organs (probably in T-cells) and in neurons. In epithelial cells, predominantly cytoplasmic. {ECO:0000269|PubMed:17164409}.; SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1, C-terminus]: Inflammasome {ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:22665479, ECO:0000269|PubMed:30291141, ECO:0000269|PubMed:33420028, ECO:0000269|PubMed:33420033}.; SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1, N-terminus]: Nucleus {ECO:0000269|PubMed:35618833}. Note=(Microbial infection) Interaction with human herpes virus 8/HHV-8 proteins ORF45 promotes translocation of the N-terminal part of NLRP1 into the nucleus, relieving autoinhibition of the NLRP1 inflammasome and leading to its activation. {ECO:0000269|PubMed:35618833}.
uniprot
proteins