Nlrp1a
entrez
195046
canonical
uniprot
Q2LKU9
canonical
ensembl
ENSMUSG00000069830
resolver
ensp
ENSMUSP00000104158
resolver
ensp
ENSMUSP00000164199
resolver
genesymbol
Nlrp1a
resolver
genesymbol_syn
Card7
resolver
genesymbol_syn
Nalp1
resolver
genesymbol_syn
Nalp1a
resolver
genesymbol_syn
Nlrp1
resolver
uniprot
M4T3K8
resolver
uniprot
M4T4C8
resolver
uniprot
M4T632
resolver
uniprot
M4TJP5
resolver
uniprot
Q3U0B5
resolver
uniprot
Q67EY4
resolver
uniprot_entry
NLR1A_MOUSE
resolver
uniprot_sec
M4T3K8
resolver
uniprot_sec
M4T4C8
resolver
uniprot_sec
M4T632
resolver
uniprot_sec
M4TJP5
resolver
uniprot_sec
Q3U0B5
resolver
uniprot_sec
Q67EY4
resolver
activity_regulation
ACTIVITY REGULATION: Nlrp1a inflammasome is 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 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (By similarity). Nlrp1a 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). {ECO:0000250|UniProtKB:Q2LKW6, ECO:0000250|UniProtKB:Q9C000, ECO:0000269|PubMed:31383852}.
uniprot
proteins
amino_acid_sequence
MEESQSKQESSTKVAQHEGQEDVDPTFKTKKLMEVELMKHRVQLERNLKLRTFPGARTKQVKEALYPLLTWSSKSKNLFQNFTKLLLFKKLCQRGSENLVRESWYPCVPEEEAHMIDIQDLFGPNLGTQKKPQLVIIEGAAGIGKSTLARLVKRAWKEGKLYRNDFHHVFFFSCRELAQYEQLSLAELIVQGQEVPTAPIRQILSHPEKLLFILDGIDEPAWVLADQNPELCLHWSQTQPVHTLLGSLLGKSILPGASFLLTTRTTALQKFIPSLEQPCQVEVLGFTLFERKNYFYKYFGKKKGGVTTFTLVKSNSALLTLCEVPWVCWLVCTCLKKQMEQGGELSLTSQTTTALCLKYLSLTIPGQHMRTQLRDLCSLAAEGVCQRRTLFSESDLCKQGLDEHAIASFLKIGVLQKQASSLSYSFAHLCLQEFFAAMSYILDDSEERHADMKNDRIVETLVERYGRQNLFEAPTVRFLFGLLSKEELKKIEKLFSCSLHGKTKLKLLWHILGKSQPHQPPCLGLLHCLYENQDMELLTHVMHDLQGTIVPGPDDLAHTVLQTNVKHLVIQTDMDLMVVTFCIKFCCHVRSLQLNRKVQQGHKFTAPGMVLYRWTPITDASWKIFFSNLKLARNLEELDLSGNPLSYYAVHSLCTTLRKRGCQLKTLWLVECGLTSTYCSLLASVLSARSSLTELDLQLNDLGDGGVKMLCEGLRNPACNLSILWLDQASLSDQVIAELRTLEAKNPKLLISSTWKPHVMVPTMNMDKEEVGDSQALLKQQRQQSGDKHMEPLGTEDEFWGPTGPVTTEVVDRERNLYRVQLPMAGSYHCPSTGLHFVVTRAVTIEIEFCAWSQYLDKTPLQQSHMVVGPLFDIKAEQGAVTAVYLPHFVALQEGIVDSSLFHVAHFQEHGMVLETPARVEQHYAVLENPSFSPMGILLRMIPAVGHFIPITSTTLIYYHLYLEDVTFHLYLVPNDCSIRKAIDDEEMKFQFVRINKPPPVDALYLGSRYIVSSSKLVEIIPKELELCYRSPGESQLFSEIDIGHMDSEIKLQIKDKRHMNLKWEALLKPGDLRPALPKIATAPKDAPSLLHFMDQHREQLVARVTSVDPLLDKLHGLVLSEDSYEVVRSETTNQDKMRKLFSLSRSWSWDCKDQFYQALKETHPHLVMDILEKLGGVSVKS
uniprot
proteins
ec_number
3.4.-.-
uniprot
proteins
function
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 (PubMed:23219391). 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 (PubMed:23219391). {ECO:0000250|UniProtKB:Q9C000, ECO:0000269|PubMed:23219391}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1a]: 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. {ECO:0000250|UniProtKB:Q9C000}.; FUNCTION: [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 (By similarity). In response to pathogen-associated signals, this part is ubiquitinated and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1a inflammasome (By similarity). {ECO:0000250|UniProtKB:Q9C000}.; FUNCTION: [NACHT, LRR and PYD domains-containing protein 1a, C-terminus]: Constitutes the active part of the Nlrp1a inflammasome (By similarity). 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q9C000}.
uniprot
proteins
mass_dalton
134308
uniprot
proteins
mutagenesis
MUTAGEN 593; /note="Q->P: Constitutively active in IL1B release. In conventional housing conditions, mice bearing this mutation develop a systemic inflammatory phenotype associated with elevated IL1B and IL18 levels at 3-5 months of age. In a germ-free environment, they exhibit neutrophilia and myocarditis."; /evidence="ECO:0000269|PubMed:23219391
uniprot
proteins
post_translational_modification
PTM: [NACHT, LRR and PYD domains-containing protein 1a]: 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 1a, N-terminus]: Ubiquitinated in response to pathogen-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 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome. {ECO:0000250|UniProtKB:Q9C000}.
uniprot
proteins
protein_family
NLRP family
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16429160
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
23219391
uniprot
proteins
pubmed
23506131
uniprot
proteins
pubmed
31383852
uniprot
proteins
sequence_length
1182
uniprot
proteins
subcellular_location
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}.
uniprot
proteins