Protein: NACHT, LRR and PYD domains-containing protein 1b allele 1 (EC 3.4.-.-) [Cleaved into: NACHT, LRR and PYD domains-containing protein 1b, C-terminus (Nlrp1b1-CT); NACHT, LRR and PYD domains-containing protein 1b, N-terminus (Nlrp1b1-NT)] (Q2LKW6)
Organism: Mus musculus (Mouse)
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. 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. Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as B.anthracis lethal toxin (LT) or Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex. 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. 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. Primary mediator of macrophage susceptibility to B.anthracis LT: in response to B.anthracis infection, macrophages and dendritic cells release IL1B and undergo pyroptosis. This early inflammatory response to the toxin increases resistance to infection by B.anthracis spores.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:19124602}. Cytoplasm, cytosol {ECO:0000269|PubMed:19124602}. Membrane {ECO:0000269|PubMed:19124602}.; SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1b, C-terminus]: Inflammasome {ECO:0000269|PubMed:24492532, ECO:0000269|PubMed:30872533}.
Interaction partners:
Sequence:
MEESPPKQKSNTKVAQHEGQQDLNTTRHMNVELKHRPKLERHLKLGMIPVVYMKQGEEILYPAQSLREENLIQNFTSLLLLQKLCPKDPENMIRKSWASCVPEEGGHMINIQDLFGPNIGTQKEPQLVIIEGAAGIGKSTLARLVKRAWKEGQLYRDHFQHVFFFSCRELAQCKKLSLAELIAQGQEVPTAPINQILSHPEKLLFILDGIDEPAWVLADQNPELCLHWSQRQPVHTLLGSLLGKSILPEAFFLLTTRTTALQKFIPSLPMPCQVEVLGFSGIERENYFYKYFANQRHAITAFMMVESNPVLLTLCEVPWVCWLVCTCLKKQMEQGRVLSLKSQTTTALCLKYLSLTIPDKHRRTQVKALCSLAAEGIWKRRTLFSESDLCKQGLDEDAVATFLKTGVLQKQASSLSYSFAHLCLQEFFAAISCILEDSEERHGNMEMDRIVETLVERYGRQNLFEAPTVRFLFGLLGKEGVKGMEKLFSCSLHGKTNLKLLWHILVKSQPHQPPCLGLLHCLYENQDMELLTHVMHDLQGTIVPGPNDTAHTVLQTNVKHLVVQTDMELMVATFCIQFYCHVRTLQLNMEKQQGYALISPRMVLYRWTPITNASWEILFYNLKFTRNLEGLDLSGNSLRYSVVQSLCNTLRYPGCQLKTLWLVKCGLTSRYCSLLASVLSAHSSLTELYLQLNDLGDDGVRMLCEGLRNPVCNLSILWLDLSSLSAQVITELRTLEEKNPKLYIRSIWMPHMMVPTENMDEEAILTTLKQQRQESGDKPMEILGTEEDFWGPTGPVATELVDRVRNLYRMPQMMVPTENMDEEDILTSFKQQRQQSGANPMEILGTEEDFWGPIGPVATEVVYRERNLYRVQLPMAGSYHCPSTRLHFVVTRAVTIEIEFCAWSQFLDKTPLQQSHMVVGPLFDIKAEQGAVTAVYLPHFVSLKDTKASTFDFKVAHFQEHGMVLETPDRVKPGYTVLKNPSFSPMGVVLRIIPAARHFIPITSITLIYYRVNQEEVTLHLYLVPNDCTIQKAIDDEEMKFQFVRINKPPPVDNLFIGSRYIVSGSENLEITPKELELCYRSSKEFQLFSEIYVGNMGSEIKLQIKNKKHMKLIWEALLKPGDLRPALPRIAQALKDAPSLLHFMDQHREQLVARVTSVDPLLDKLHGLVLNEESYEAVRAENTNQDKMRKLFNLSRSWSRACKDLFYQALKETHPHLVMDLLEKSGGVSLGS