Protein: NACHT, LRR and PYD domains-containing protein 1a (EC 3.4.-.-) (Caspase recruitment domain-containing protein 7) (Death effector filament-forming ced-4-like apoptosis protein) (Nucleotide-binding domain and caspase recruitment domain) [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)] (Q2LKU9)
Organism: Mus musculus (Mouse)
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, and mediates the formation of the inflammasome polymeric complex (By similarity). 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 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 (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). Activation of Nlrp1a inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (By similarity). When activated in the bone marrow, induces the pyroptosis of hematopoietic stem cells and progenitor cells of both myeloid and lymphoid lineages, hence allowing the removal of damaged cells, and the release of IL1B, which induces granulopoiesis.
Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9C000}. Cytoplasm {ECO:0000250|UniProtKB:Q9C000}. Nucleus {ECO:0000250|UniProtKB:Q9C000}. Note=Nucleocytoplasmic distribution in lymphoid organs (probably in T-cells) and in neurons. In epithelial cells, predominantly cytoplasmic. {ECO:0000250|UniProtKB:Q9C000}.; SUBCELLULAR LOCATION: [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q9C000}.
Interaction partners:
- Interferon-inducible protein AIM2
- Pyrin
- Caspase-1
- NLR family CARD domain-containing protein 4
- Apoptosis-associated speck-like protein containing a CARD
- Caspase-4
- NACHT, LRR and PYD domains-containing protein 6
- Nucleotide-binding oligomerization domain-containing protein 2
- NACHT, LRR and PYD domains-containing protein 3
- Apoptosis regulator Bcl-2
Sequence:
MEESQSKQESSTKVAQHEGQEDVDPTFKTKKLMEVELMKHRVQLERNLKLRTFPGARTKQVKEALYPLLTWSSKSKNLFQNFTKLLLFKKLCQRGSENLVRESWYPCVPEEEAHMIDIQDLFGPNLGTQKKPQLVIIEGAAGIGKSTLARLVKRAWKEGKLYRNDFHHVFFFSCRELAQYEQLSLAELIVQGQEVPTAPIRQILSHPEKLLFILDGIDEPAWVLADQNPELCLHWSQTQPVHTLLGSLLGKSILPGASFLLTTRTTALQKFIPSLEQPCQVEVLGFTLFERKNYFYKYFGKKKGGVTTFTLVKSNSALLTLCEVPWVCWLVCTCLKKQMEQGGELSLTSQTTTALCLKYLSLTIPGQHMRTQLRDLCSLAAEGVCQRRTLFSESDLCKQGLDEHAIASFLKIGVLQKQASSLSYSFAHLCLQEFFAAMSYILDDSEERHADMKNDRIVETLVERYGRQNLFEAPTVRFLFGLLSKEELKKIEKLFSCSLHGKTKLKLLWHILGKSQPHQPPCLGLLHCLYENQDMELLTHVMHDLQGTIVPGPDDLAHTVLQTNVKHLVIQTDMDLMVVTFCIKFCCHVRSLQLNRKVQQGHKFTAPGMVLYRWTPITDASWKIFFSNLKLARNLEELDLSGNPLSYYAVHSLCTTLRKRGCQLKTLWLVECGLTSTYCSLLASVLSARSSLTELDLQLNDLGDGGVKMLCEGLRNPACNLSILWLDQASLSDQVIAELRTLEAKNPKLLISSTWKPHVMVPTMNMDKEEVGDSQALLKQQRQQSGDKHMEPLGTEDEFWGPTGPVTTEVVDRERNLYRVQLPMAGSYHCPSTGLHFVVTRAVTIEIEFCAWSQYLDKTPLQQSHMVVGPLFDIKAEQGAVTAVYLPHFVALQEGIVDSSLFHVAHFQEHGMVLETPARVEQHYAVLENPSFSPMGILLRMIPAVGHFIPITSTTLIYYHLYLEDVTFHLYLVPNDCSIRKAIDDEEMKFQFVRINKPPPVDALYLGSRYIVSSSKLVEIIPKELELCYRSPGESQLFSEIDIGHMDSEIKLQIKDKRHMNLKWEALLKPGDLRPALPKIATAPKDAPSLLHFMDQHREQLVARVTSVDPLLDKLHGLVLSEDSYEVVRSETTNQDKMRKLFSLSRSWSWDCKDQFYQALKETHPHLVMDILEKLGGVSVKS