The following text describes a protein:
Function:
Acts as the sensor component of the Nlrp1a 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, such as Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex. In response to pathogen-associated signals, the N-terminal part of Nlrp1a is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, 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 Nlrp1a inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME) (By similarity); [NACHT, LRR and PYD domains-containing protein 1a allele 5]: Constitutes the precursor of the Nlrp1a 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; [NACHT, LRR and PYD domains-containing protein 1a, N-terminus]: Regulatory part that prevents formation of the Nlrp1a inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), preventing activation of the Nlrp1a 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 Nlrp1a inflammasome; [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]: Constitutes the active part of the Nlrp1a inflammasome. In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, N-terminus), preventing activation of the Nlrp1a inflammasome. In response to pathogen-associated signals, the N-terminal part of Nlrp1a is degraded by the proteasome, releasing this form, which polymerizes to form the Nlrp1a inflammasome complex: the Nlrp1a inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis.
Subcellular Localization:
Cytoplasm, cytosol. Cytoplasm. Nucleus; [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]: Inflammasome.
Domain:
The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain; The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding. Autocatalytic cleavage in this 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 fragments remain associated; [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]: The C-terminal part of Nlrp1a oligomerizes to form the core of the Nlrp1a inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments. The UPA region reduces the threshold needed for filament formation and signaling.
Sequence:
MGESQSKQESNTRVAQHGSQQDVDPTFQTKRALERERSSPQVEQSFLGQLQSLLGWSSTSKDVPLSQLIREMDHESRRHSHQSKKKLDRSEHISEGTIPEIYEKRKETISHTQSMEQKYLFQNFTKLLLLQKCCPGGSEKLVRESWHPCVPEEGGHMIEIQDLFDPNLDTEKKPQLVIIEGAAGIGKSTLARQVKRAWEEGQLYRDRFQHVFFFSCRELAQCKQLSLAELIAQGQEVLTAPTRQILSRPEKLLFILDGIDEPAWVLEDQNPELCVHWSQAQPVHTLLGSLLGKSILPEASLMLTARTTALQKLIPSLGQPHRVEVLGFSEFERKDYFYKYFAKERNTIIDFNLIGSIPVLLTLCEVPWVCWLLCTCLEKQMQQGEVLSLTSQTTTALCLKYLSLTIPGQHLSTQLRTLCSLAAEGICQRRTLFSKSDLCKQGLAEDAIATFLKIGVLQRQPSSLSYSFAHLCLQEFFAAMSYILEDSEEARGDMGNDRTVETLVERYGRQNLFEAPTVRFLLGLLNTREMREMENIFACKFPWKTKLKLLRSIVGEPFCQPCHLGLFHCLYENQEEELLTETMLCFPLTASGPNHMEATVFQTNVKRLVIQTDMELMVVTFCITFSHVRSLRLKGKGQQEYKLTAPAMVLYRWTPISEASWKVLFSNLKCTRNLEELDLSGNPLSYSAVRSLCTALRQPGCRLKTLWLVDCGLTSRCCSFLASMLSAHSRLAELDLRLNDLGDNGVRQLCEGLRNPACNLSILRLDQASLSEQVITELRALETKNPKLFISSTWMSHMTMPTENTDGEESLTSSKQQQQQSGDKHMEPLGTDDDFWGPSGPVSTEVVDRERNLYRVRLPMAGSYHCPSTGLHFVVTRAVTIEIGFCAWSQFLHETPLQHSHMVAGPLFDIKAEHGAVTAVCLPHFVSLQEGKVDSSLFHVAHFQDHGMVLETPARVEPHFAVLENPSFSPMGVLLRMIPAVGHFIPITSITLIYYRLYLEDITFHLYLVPNDCTIRKAIDEEELKFQFVRINKPPPVDALYVGSRYIVSSSKEVEILPKELELCYRSPRESQLFSEIYVGNIGSGINLQLTDKKYMNLIWEALLKPGDLRPALPRMASAPKDAPALLHFVDQHREQLVARVTSVDPLLDKLHGLVLSEEDYETVRAEATNQDKMRKLFRGSRSWSWDCKDHFYQALKETHPHLIMDLLEKSGGVSVRL