Nlrp1b
entrez
637515
canonical
uniprot
A1Z198
canonical
ensembl
ENSMUSG00000070390
resolver
ensp
ENSMUSP00000104155
resolver
ensp
ENSMUSP00000104156
resolver
genesymbol
Nlrp1b
resolver
genesymbol_syn
Nalp1b
resolver
uniprot
F6R9S5
resolver
uniprot
Q2LK61
resolver
uniprot
Q2LKV8
resolver
uniprot_entry
NL1B2_MOUSE
resolver
uniprot_sec
F6R9S5
resolver
uniprot_sec
Q2LK61
resolver
uniprot_sec
Q2LKV8
resolver
activity_regulation
ACTIVITY REGULATION: Activated by pathogens and other damage-associated signals: activation 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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (By similarity). Nlrp1b inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b oligomerization and activation (By similarity). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). May be activated by Toxoplasma gondii, although at a lower extent than allele 1 (PubMed:24218483). Not activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160, PubMed:21170303, PubMed:24492532, PubMed:31383852). May be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000250|UniProtKB:Q9C000, ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:18511561, ECO:0000269|PubMed:21170303, ECO:0000269|PubMed:24218483, ECO:0000269|PubMed:24492532, ECO:0000269|PubMed:31383852}.
uniprot
proteins
amino_acid_sequence
MEESQYKQEHNKKVAQDEGQEDKDTIFETIEAIEAKLMELKTNPESTFNYGIFPEVYMNQGEEILYPAWSLKEENLFQTFKSLRLFQKLCPRGSGNLVKKSWYPCVPEEGGHIINIQDLFGPNIGTQKEPQLVIIEGAAGIGKSTLARQVKRAWMEGELYRDHFQHVFFFSCRELAQCKKLSLAELITQGQDVPTAPINQILSHPEKLLFILDGIDEPAWVLADQNPELCLYWSQTQPVHTLLGSLLGKSILPEASFLLTTRTTALQKFIPSLPQSCQVEVLGFSDFEQEIYIYKYFAKQIFGIKALMMVESNPVLLTLCEVPWVCWLVCNCLKKQMEQGGDVSLTSQTTTAICLKYISLTIPVHHMRTQLRALCSLAAEGIWKRRTLFSESDLCKQGLDEDAVAIFLKTGVLQKQASSLSYSFAHLCLQEFFASMSCILEDSEERHGDMEMDRIVETLVERYGRQNLFEAPTVRFLFGLLSKEGLKEMEKLFSCSLPGKTKLKLLWHILGKSQPHQPPCLGLLHCLYENQDMKLLTHVMHDLQGTIVPDTDDITHTVLQTNVKHLVVRTDMELMVVTFCIQFCSHMRSLQLNMEGQQGYALTAPRMVLYRWTPITNASWKILFYNLKFNSNLEGLDLSGNPLSYSAVQYLCDAMIYPGCQLKTLWLVECGLTPTYCSLLASVLSACSSLRELDLQLNDLCDDGVRMLCEGLRNRACNLRILRLDLYSLSAQVITELRTLEENNLKLHISSIWMPQMMVPTENMDEEDILTSFKQQRQQSGANPMEILGTEEDFWGPIGPVATEVVYRERNLYRVQLPMAGSYHCPSTRLHFVVTRAVTIEIEFCAWSQFLDKTPLQQSHMVVGPLFDIKAEQGAVTAVYLPHFVSLKDTKASTFDFKVAHFQEHGMVLETPDRVKPGYTVLKNPSFSPMGVVLRIIPAARHFIPITSITLIYYRVNQEEVTLHLYLVPNDCTIQKAIDDEEMKFQFVRINKPPPVDNLFIGSRYIVSGSENLEITPKELELCYRSSKEFQLFSEIYVGNMGSEIKLQIKNKKHMKLIWEALLKPGDLRPALPRIAQALKDAPSLLHFMDQHREQLVARVTSVDPLLDKLHGLVLNEESYEAVRAENTNQDKMRKLFNLSRSWSRACKDLFYQALKETHPHLVMDLLEKSGGVSLGS
uniprot
proteins
ec_number
3.4.-.-
uniprot
proteins
function
FUNCTION: Acts as the sensor component of the Nlrp1b inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (By similarity). 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 (By similarity). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals: in response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the inflammasome directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (By similarity). In the absence of GSDMD expression, the Nlrp1b inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME) (By similarity). Activation of Nlrp1b inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (By similarity). Contrary to Nlrp1b allele 1, allele 2 is not activated by Bacillus anthracis lethal toxin (PubMed:16429160, PubMed:21170303, PubMed:24492532). {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000269|PubMed:16429160, ECO:0000269|PubMed:21170303, ECO:0000269|PubMed:24492532}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b allele 2]: Constitutes the precursor of the Nlrp1b 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:0000250|UniProtKB:Q2LKW6}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]: Regulatory part that prevents formation of the Nlrp1b inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), preventing activation of the Nlrp1b inflammasome. In response to pathogen-associated signals, this part is ubiquitinated by the N-end rule pathway and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1b inflammasome. {ECO:0000250|UniProtKB:Q2LKW6}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1b, C-terminus]: Constitutes the active part of the Nlrp1b inflammasome. In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus), preventing activation of the Nlrp1b inflammasome. In response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing this form, which polymerizes to form the Nlrp1b inflammasome complex: the Nlrp1b inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis. {ECO:0000250|UniProtKB:Q2LKW6}.
uniprot
proteins
mass_dalton
134163
uniprot
proteins
post_translational_modification
PTM: [NACHT, LRR and PYD domains-containing protein 1b allele 2]: Autocatalytically cleaved. Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal parts remain associated non-covalently. {ECO:0000305|PubMed:31383852}.; PTM: [NACHT, LRR and PYD domains-containing protein 1b, N-terminus]: Ubiquitinated by the N-end rule pathway in response to pathogens and other damage-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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome. {ECO:0000250|UniProtKB:Q2LKW6}.
uniprot
proteins
protein_family
NLRP family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16429160
uniprot
proteins
pubmed
18511561
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21170303
uniprot
proteins
pubmed
23506131
uniprot
proteins
pubmed
24218483
uniprot
proteins
pubmed
24492532
uniprot
proteins
pubmed
26253422
uniprot
proteins
pubmed
31383852
uniprot
proteins
pubmed
32558991
uniprot
proteins
sequence_length
1177
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q2LKW6}.; SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1b, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q2LKW6}.
uniprot
proteins