Protein: NACHT, LRR and PYD domains-containing protein 1a allele 1 (EC 3.4.-.-) [Cleaved into: NACHT, LRR and PYD domains-containing protein 1a, C-terminus (Nlrp1a-CT); NACHT, LRR and PYD domains-containing protein 1a, N-terminus (Nlrp1a-NT)] (D9I2F9)
Organism: Rattus norvegicus (Rat)
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. 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 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 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).
Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9C000}. Cytoplasm {ECO:0000250|UniProtKB:Q9C000}. Nucleus {ECO:0000250|UniProtKB:Q9C000}.; SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q9C000}.
InterPro domains:
- IPR032675: Leucine-rich repeat domain superfamily (homologous_superfamily) [612-797]
- IPR011029: Death-like domain superfamily (homologous_superfamily) [1124-1212]
- IPR001315: CARD domain (domain) [1122-1211]
- IPR033516: CARD8/ASC/NALP1, CARD domain (domain) [1128-1208]
- IPR041075: NOD1/2, winged helix domain (domain) [414-468]
- IPR007111: NACHT nucleoside triphosphatase (domain) [175-484]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [79-379]
- IPR025307: FIIND domain (domain) [835-1118]
- IPR001611: Leucine-rich repeat (repeat) [672-750]
- IPR041267: NACHT, LRR and PYD domains-containing protein, helical domain HD2 (domain) [470-581]
- IPR051249: NLRP Inflammasome (family) [9-1210]
Sequence:
MEESQSKQESNTRVAQHGSQQDVDPTFQTKRALEKERSKPRPRPLPRVQLQSLPGWSSTSNDVPLSQLIREMDHESRRCIHRSKKKLDRSEHISQGTIPEIYEKRKETISHTQSMEQKYLFQNFTKLLLLQKCCPGGSEKLVRESWHPCVPEEGGHMIEIQDLFDPNLDTEKKPQLVIIEGAAGIGKSTLARQVKRAWDEGQLYRDRFQHVFFFSCRELAQCKQLSLAELIAQGQEVPTAPTRQILSRPEKLLFILDGIDEPAWVLEDQNPELCVHWSQAQPVHTLLGSLLGKSILPEASLMLTARTTALQKLVPSLGQPHRVEVLGFSEFERKDYFYKYFAKERNTIIDFNLIGSIPVLLTLCEVPWVCWLLCTCLEKQMQQGEVLSLTSQTTTALCLKYLSLTIPGQHLSTQLRTLCSLAAEGICQRRTLFSKSDLCKQGLAEDAIATFLKIGVLQRQPSSLSYSFAHLCLQEFFAAMSYILEDSEEAHGDMGNDRTVETLVERYGRQNLFEAPTVRFLLGLLNTREMREMENIFACKFPWETKLKLLQSIIGEPFCQPCHLGLFHCLYENQEEELLTETMLCFPLTASGPNHMEATVFQTNVKRLVIQTDMELMVVTFCITFSHVRSLRLKGKGQQEYKLTAPAMVLYRWTPISEASWKVLFSNLKCTRNLEELDLSGNPLSYSAVRSLCTALRQPGCRLKTLWLVDCGLTSRCCSFLASMLSAHSRLAELDLRLNDLGDNGVRQLCEGLRNPACNLSILRLDQASLSEQVITELRALETKNPKLFISSTWMSHMTMPTENTDGEESLTSSKQQQQQSGDKHMEPLGTDDDFWGPSGPVSTEVVDRERNLYRVRLPMAGSYHCPSTGLHFVVTRAVTIEIGFCAWSQFLHETPLQHSHMVAGPLFDIKAEHGAVTAVCLPHFVSLQEGKVDSSLFHVAHFQDHGMVLETPARVEPHFAVLENPSFSPMGVLLRMIPAVGHFIPITSITLIYYRLYLEDITFHLYLVPNDCTIRKAIDEEELKFQFVRINKPPPVDALYVGSRYIVSSSKEVEILPKELELCYRSPRESQLFSEIYVGNIGSGINLQLTDKKYMNLIWEALLKPGDLRPALPRMASAPKDAPALLHFVDQHREQLVARVTSVDPLLDKLHGLVLSEEDYETVRAEATNQDKMRKLFRGSRSWSWDCKDHFYQALKETHPHLIMDLLEKSGGVSVRL
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0097110 (scaffold protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0048583 (regulation of response to stimulus), GO:0048585 (negative regulation of response to stimulus), GO:0050794 (regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0010942 (positive regulation of cell death), GO:0031348 (negative regulation of defense response), GO:0010941 (regulation of cell death), GO:0080134 (regulation of response to stress), GO:0031347 (regulation of defense response), GO:0043067 (regulation of programmed cell death), GO:0043068 (positive regulation of programmed cell death)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:0036477 (somatodendritic compartment), GO:0044297 (cell body), GO:0043025 (neuronal cell body)