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Entry version 97 (02 Jun 2021)
Sequence version 1 (21 Feb 2006)
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Protein

NACHT, LRR and PYD domains-containing protein 1b allele 1

Gene

Nlrp1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Acts as the sensor component of the Nlrp1b inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (PubMed:19651869, PubMed:21170303, PubMed:22536155, PubMed:22753929, PubMed:23818853).

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 (PubMed:19651869, PubMed:21170303, PubMed:22536155, PubMed:22753929, PubMed:23818853, PubMed:31268597, PubMed:30872533, PubMed:30872531).

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 (PubMed:31268597, PubMed:30872533, PubMed:30872531).

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 (PubMed:16429160, PubMed:19949100, PubMed:22753929, PubMed:23818853, PubMed:31268597, PubMed:30872533, PubMed:30872531).

Activation of Nlrp1b inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (PubMed:22801494).

Primary mediator of macrophage susceptibility to B.anthracis LT: in response to B.anthracis infection, macrophages and dendritic cells release IL1B and undergo pyroptosis (PubMed:16429160, PubMed:19949100, PubMed:22753929, PubMed:23818853).

This early inflammatory response to the toxin increases resistance to infection by B.anthracis spores (PubMed:16429160, PubMed:19949100, PubMed:22753929, PubMed:23818853).

11 Publications

Constitutes the precusor of the Nlrp1b 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.

1 Publication

Regulatory part that prevents formation of the Nlrp1b inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), preventing activation of the Nlrp1b inflammasome (PubMed:30872533, PubMed:30872531).

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 Nlrp1b inflammasome (PubMed:30872533, PubMed:30872531).

2 Publications

Constitutes the active part of the Nlrp1b inflammasome (PubMed:30872533, PubMed:30872531).

In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus), preventing activation of the Nlrp1b inflammasome (PubMed:30872533, PubMed:30872531).

In response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing this form, which polymerizes to form the Nlrp1b inflammasome complex: the Nlrp1b inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis (PubMed:31268597, PubMed:30872533, PubMed:30872531).

3 Publications

Miscellaneous

Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c, have been identified. Nlrp1c is predicted to be a pseudogene. Neither Nlrp1a, nor Nrlp1c are expressed in anthrax lethal toxin susceptible strains, hence neither of them is thought to play an important role in this phenotype.1 Publication1 Publication
In macrophages and dendritic cells, NLRP1 inflammasome activation of CASP1 and IL1B maturation can be dampened by direct contact with activated effector and memory T-cells. This effect may be mediated by hexameric TNF ligands, such as CD40LG.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase: cleavage by LT 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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (PubMed:19124602, PubMed:19651869, PubMed:19949100, PubMed:22536155, PubMed:23818853, PubMed:24492532, PubMed:24935976, PubMed:31383852, PubMed:30872531). Activated by S.flexneri IpaH7.8, an E3 ubiquitin ligase that mediates ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1b inflammasome (PubMed:30872533). Nlrp1b inflammasome is inhibited by DPP8 and DPP9 via an unknown mechanism (PubMed:29396289, PubMed:31525884). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:29396289, PubMed:31525884, PubMed:31383852, PubMed:30872531). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by inducing the proteasome-mediated destruction of the N-terminal part of Nlrp1b, releasing its C-terminal part from autoinhibition (PubMed:29396289, PubMed:31525884, PubMed:30872531). Activated by metabolic inhibitors, such as 2-deoxy-D-glucose and sodium azide, by nutrient deprivation and hypoxia, possibly due to a decrease in cytosolic ATP (PubMed:24935976, PubMed:23230290). Also activated by Toxoplasma gondii (PubMed:24218483). Not activated by muramyl dipeptide, nor by full-length bacterial peptidoglycan (PubMed:22753929). Contrary to its human ortholog, not activated by positive-strand RNA virus such as Semliki Forrest virus or long dsRNA (PubMed:33243852).16 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei44 – 45(Microbial infection) Probable cleavage; by anthrax lethal toxin (LT) endopeptidase component1 Publication2

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi132 – 139ATPPROSITE-ProRule annotation8

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionHydrolase, Protease
Biological processImmunity, Inflammatory response, Innate immunity, Necrosis
LigandATP-binding, Nucleotide-binding

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
NACHT, LRR and PYD domains-containing protein 1b allele 11 Publication (EC:3.4.-.-1 Publication)
Cleaved into the following 2 chains:
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Nlrp1b1 Publication
Synonyms:Nalp1b1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:3582959, Nlrp1b

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Inflammasome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

No visible phenotype under usual housing conditions. When challenged with intratracheal instillation of B.anthracis lethal toxin (LT), mutant animals are protected from lung damages caused by sustained inflammation. Macrophages isolated from mutant animals are resistant LT.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi1 – 50Missing : Low spontaneous IL1B release and loss of activation by LT. Increased IL1B release in response to metabolic inhibitors. 1 PublicationAdd BLAST50
Mutagenesisi1 – 44Missing : Low spontaneous IL1B release and loss of activation by LT. No effect on activation by metabolic inhibitors. 1 PublicationAdd BLAST44
Mutagenesisi1 – 40Missing : No effect on IL1B release. 1 PublicationAdd BLAST40
Mutagenesisi34 – 36KHR → AAA: No effect on cleavage by LT, nor on IL1B processing. No effect on cleavage by LT, nor on IL1B processing; when associated with 38-A-A-39. 1 Publication3
Mutagenesisi37 – 39PKL → QAQ: No effect on cleavage by LT. 1 Publication3
Mutagenesisi38 – 39KL → AA: No effect on cleavage by LT, nor on IL1B processing. 1 Publication2
Mutagenesisi43L → Q: Loss of cleavage by LT and of LT-induced IL1B processing and suppression of LT-induced pyroptosis in macrophages, no effect on IL1B release in response to metabolic inhibitors; when associated with A-44 and Q-45. 2 Publications1
Mutagenesisi44K → A: Partial loss of cleavage by LT and of LT-induced IL1B processing. Loss of cleavage by LT and of LT-induced IL1B processing; when associated with Q-43 and Q-45. No effect on IL1B release in response to metabolic inhibitors; when associated with Q-43 and Q-45. 2 Publications1
Mutagenesisi45L → Q: Loss of cleavage by LT and of LT-induced IL1B processing. Loss of cleavage by LT and of LT-induced IL1B processing; when associated with Q-43 and A-44. No effect on IL1B release in response to metabolic inhibitors; when associated with Q-43 and A-44. 2 Publications1
Mutagenesisi137 – 139GKS → AAA: Constitutive IL1B release. 1 Publication3
Mutagenesisi626 – 719Missing : Constitutive IL1B processing. 1 PublicationAdd BLAST94
Mutagenesisi629E → A: Increased IL1B release under basal conditions. No effect on IL1B release in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi632D → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT; when associated with A-634. 1 Publication1
Mutagenesisi634S → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT; when associated with A-632. 1 Publication1
Mutagenesisi644Q → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi648N → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi651R → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi658K → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT; when associated with A-659. 1 Publication1
Mutagenesisi659T → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT; when associated with A-658. 1 Publication1
Mutagenesisi661W → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi663V → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors, no effect on the response to LT; when associated with A-664. 1 Publication1
Mutagenesisi664K → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors, no effect on the response to LT; when associated with A-663. 1 Publication1
Mutagenesisi670R → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi673S → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi686T → A: Spontaneous IL1B release under basal conditions, no effect on the response to metabolic inhibitors, partial loss of response to LT; when associated with A-687. 1 Publication1
Mutagenesisi687E → A: Spontaneous IL1B release under basal conditions, no effect on the response to metabolic inhibitors, partial loss of response to LT; when associated with A-686. 1 Publication1
Mutagenesisi689Y → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi691Q → A: Low spontaneous IL1B release, no effect on the response to metabolic inhibitors, nor to LT. 1 Publication1
Mutagenesisi698D → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors; when associated with A-701 and A-702. 1 Publication1
Mutagenesisi701R → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors; when associated with A-698 and A-702. 1 Publication1
Mutagenesisi702M → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors; when associated with A-698 and A-701. 1 Publication1
Mutagenesisi705E → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi720D → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT. 1 Publication1
Mutagenesisi727Q → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi731E → A: Increased IL1B release under basal conditions. No effect on IL1B release in response to LT or metabolic inhibitors. 1 Publication1
Mutagenesisi734T → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors; when associated with A-738. 1 Publication1
Mutagenesisi738K → A: No effect on IL1B release under basal conditions, nor in response to LT or metabolic inhibitors; when associated with A-734. 1 Publication1
Mutagenesisi744I → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT; when associated with A-746. 1 Publication1
Mutagenesisi746S → A: Spontaneous IL1B release under basal conditions, loss of response to metabolic inhibitors and to LT; when associated with A-744. 1 Publication1
Mutagenesisi749 – 809Missing : No effect on response to LT, attenuated response to metabolic inhibitors. 1 PublicationAdd BLAST61
Mutagenesisi810 – 870Missing : No effect on response to LT, attenuated response to metabolic inhibitors. 1 PublicationAdd BLAST61
Mutagenesisi984S → A: Loss of autocatalytic cleavage within the FIIND region, abolishing the ability to activate the inflammasome. Abolished interaction with DPP9. No effect on cleavage by LT. 3 Publications1
Mutagenesisi988V → D: Loss of autocatalytic cleavage within the FIIND region and of IL1B release, decrease in CASP1-binding. No effect on homomerization. 1 Publication1
Mutagenesisi996A → D: Strong decrease of IL1B release, but no effect on autocatalytic cleavage within the FIIND region. 1 Publication1
Mutagenesisi1012V → L: No effect on autocatalytic cleavage within the FIIND region. 1 Publication1
Mutagenesisi1014Q → L: No effect on autocatalytic cleavage within the FIIND region. 1 Publication1
Mutagenesisi1026N → S: Decrease of IL1B release, but no effect on autocatalytic cleavage within the FIIND region. 1 Publication1
Mutagenesisi1100 – 1106EIKLQIK → AAAAAAA: Loss of homomerization, of autocatalytic cleavage within the FIIND region and of IL1B release. No effect on CASP1-binding. 1 Publication7
Mutagenesisi1112K → R: No effect on autocatalytic cleavage within the FIIND region. 1 Publication1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004351031 – 1233NACHT, LRR and PYD domains-containing protein 1b allele 1Add BLAST1233
ChainiPRO_00004528551 – 983NACHT, LRR and PYD domains-containing protein 1b, N-terminus1 PublicationAdd BLAST983
ChainiPRO_0000452856984 – 1233NACHT, LRR and PYD domains-containing protein 1b, C-terminus1 PublicationAdd BLAST250

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Autocatalytically cleaved (PubMed:23818853). 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 (PubMed:23818853).1 Publication
Ubiquitinated by UBR2, a component of the N-end rule pathway in response to pathogens and other damage-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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome.2 Publications
(Microbial infection) Cleavage by B.anthracis lethal toxin (LT) endopeptidase 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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome.8 Publications
(Microbial infection) Ubiquitinated by S.flexneri IpaH7.8, 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 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei983 – 984Cleavage; by autolysisPROSITE-ProRule annotation1 Publication2

Keywords - PTMi

Ubl conjugation

Proteomic databases

PRoteomics IDEntifications database

More...
PRIDEi
Q2LKW6

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed, including in macrophages.2 Publications

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with DPP8; leading to inhibit activation of the inflammasome via an unknown mechanism (PubMed:31525884).

Interacts with DPP9; leading to inhibit activation of the inflammasome via an unknown mechanism (PubMed:31525884).

Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3) (By similarity).

Interacts with NOD2; this interaction may increase IL1B release (By similarity).

Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to B.anthracis lethal toxin (PubMed:22801494).

Interacts with MEFV; this interaction targets Nlrp1b to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity).

By similarity2 Publications

Interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in absence of pathogens and other damage-associated signals.

2 Publications

Interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus) in absence of pathogens and other damage-associated signals (PubMed:30872533, PubMed:30872531). Homomultimer; forms the Nlrp1b inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals (PubMed:19124602, PubMed:19651869, PubMed:22536155, PubMed:24492532, PubMed:30872533, PubMed:30872531). The Nlrp1b inflammasome polymeric complex directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC (PubMed:19124602, PubMed:19651869, PubMed:24492532).

Interacts (via CARD domain) with CASP1 (via CARD domain); leading to CASP1 activation (PubMed:19651869).

6 Publications

GO - Molecular functioni

Protein-protein interaction databases

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-4261, NLRP1b inflammasome, allele-1 variant

Protein interaction database and analysis system

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IntActi
Q2LKW6, 1 interactor

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q2LKW6

Database of comparative protein structure models

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ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini126 – 435NACHTPROSITE-ProRule annotationAdd BLAST310
<p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati627 – 647LRR 1Add BLAST21
Repeati684 – 704LRR 2Add BLAST21
Domaini850 – 1133FIINDPROSITE-ProRule annotationAdd BLAST284
Domaini1143 – 1226CARDPROSITE-ProRule annotationAdd BLAST84

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 22DisorderedSequence analysisAdd BLAST22
Regioni850 – 983ZU5By similarityAdd BLAST134
Regioni984 – 1133UPABy similarityAdd BLAST150

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi8 – 22Polar residuesSequence analysisAdd BLAST15

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The CARD domain is involved in the interaction with CASP1 and CASP4/CASP11.By similarity
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.3 Publications
The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding (PubMed:22536155). 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 (PubMed:22536155, PubMed:23818853).2 Publications
The C-terminal part of Nlrp1b oligomerizes to form the core of the Nlrp1b 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.By similarity

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the NLRP family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Family and domain databases

Conserved Domains Database

More...
CDDi
cd08330, CARD_ASC_NALP1, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.80.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR001315, CARD
IPR033516, CARD8/ASC/NALP1_CARD
IPR011029, DEATH-like_dom_sf
IPR025307, FIIND_dom
IPR032675, LRR_dom_sf
IPR007111, NACHT_NTPase
IPR041267, NLRP_HD2
IPR041075, NOD2_WH
IPR027417, P-loop_NTPase

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00619, CARD, 1 hit
PF13553, FIIND, 1 hit
PF05729, NACHT, 1 hit
PF17776, NLRC4_HD2, 1 hit
PF17779, NOD2_WH, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF47986, SSF47986, 1 hit
SSF52540, SSF52540, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50209, CARD, 1 hit
PS51830, FIIND, 1 hit
PS51450, LRR, 2 hits
PS50837, NACHT, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

Q2LKW6-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEESPPKQKS NTKVAQHEGQ QDLNTTRHMN VELKHRPKLE RHLKLGMIPV
60 70 80 90 100
VYMKQGEEIL YPAQSLREEN LIQNFTSLLL LQKLCPKDPE NMIRKSWASC
110 120 130 140 150
VPEEGGHMIN IQDLFGPNIG TQKEPQLVII EGAAGIGKST LARLVKRAWK
160 170 180 190 200
EGQLYRDHFQ HVFFFSCREL AQCKKLSLAE LIAQGQEVPT APINQILSHP
210 220 230 240 250
EKLLFILDGI DEPAWVLADQ NPELCLHWSQ RQPVHTLLGS LLGKSILPEA
260 270 280 290 300
FFLLTTRTTA LQKFIPSLPM PCQVEVLGFS GIERENYFYK YFANQRHAIT
310 320 330 340 350
AFMMVESNPV LLTLCEVPWV CWLVCTCLKK QMEQGRVLSL KSQTTTALCL
360 370 380 390 400
KYLSLTIPDK HRRTQVKALC SLAAEGIWKR RTLFSESDLC KQGLDEDAVA
410 420 430 440 450
TFLKTGVLQK QASSLSYSFA HLCLQEFFAA ISCILEDSEE RHGNMEMDRI
460 470 480 490 500
VETLVERYGR QNLFEAPTVR FLFGLLGKEG VKGMEKLFSC SLHGKTNLKL
510 520 530 540 550
LWHILVKSQP HQPPCLGLLH CLYENQDMEL LTHVMHDLQG TIVPGPNDTA
560 570 580 590 600
HTVLQTNVKH LVVQTDMELM VATFCIQFYC HVRTLQLNME KQQGYALISP
610 620 630 640 650
RMVLYRWTPI TNASWEILFY NLKFTRNLEG LDLSGNSLRY SVVQSLCNTL
660 670 680 690 700
RYPGCQLKTL WLVKCGLTSR YCSLLASVLS AHSSLTELYL QLNDLGDDGV
710 720 730 740 750
RMLCEGLRNP VCNLSILWLD LSSLSAQVIT ELRTLEEKNP KLYIRSIWMP
760 770 780 790 800
HMMVPTENMD EEAILTTLKQ QRQESGDKPM EILGTEEDFW GPTGPVATEL
810 820 830 840 850
VDRVRNLYRM PQMMVPTENM DEEDILTSFK QQRQQSGANP MEILGTEEDF
860 870 880 890 900
WGPIGPVATE VVYRERNLYR VQLPMAGSYH CPSTRLHFVV TRAVTIEIEF
910 920 930 940 950
CAWSQFLDKT PLQQSHMVVG PLFDIKAEQG AVTAVYLPHF VSLKDTKAST
960 970 980 990 1000
FDFKVAHFQE HGMVLETPDR VKPGYTVLKN PSFSPMGVVL RIIPAARHFI
1010 1020 1030 1040 1050
PITSITLIYY RVNQEEVTLH LYLVPNDCTI QKAIDDEEMK FQFVRINKPP
1060 1070 1080 1090 1100
PVDNLFIGSR YIVSGSENLE ITPKELELCY RSSKEFQLFS EIYVGNMGSE
1110 1120 1130 1140 1150
IKLQIKNKKH MKLIWEALLK PGDLRPALPR IAQALKDAPS LLHFMDQHRE
1160 1170 1180 1190 1200
QLVARVTSVD PLLDKLHGLV LNEESYEAVR AENTNQDKMR KLFNLSRSWS
1210 1220 1230
RACKDLFYQA LKETHPHLVM DLLEKSGGVS LGS
Length:1,233
Mass (Da):140,688
Last modified:February 21, 2006 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iECB340C9A58BAFCD
GO

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Nlrp1b gene is extremely polymorphic. 5 alleles have been described in 18 inbred strains: 1 (this entry), 2 (AC A1Z198), 3 (AC Q2LKV5), 4 (AC Q2LKV2) and 5 (AC Q0GKD5). These alleles define susceptibility to B.anthracis lethal toxin (LT). Alleles 1 (carried by strains 129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO (NZO/HlLtJ) and SWR/J) and 5 (CAST/EiJ) confer macrophage susceptibility to LT. Strains with macrophages resistant to anthrax LT carry alleles 2 (A/J, C57BL/6J and I/LnJ), 3 (AKR/J, NOD/LtJ and SJL/J) or 4 (DBA/2J, P/J and SM/J). Sensitivity to LT leads to IL1B release, macrophage pyroptosis and neutrophil recruitment. This early inflammatory response confers increased resistance to infection by B. anthracis spores (PubMed:16429160, PubMed:19949100, PubMed:21170303). The sequence shown in this entry is that of allele 1 (PubMed:16429160).1 Publication3 Publications

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
DQ117583 mRNA Translation: AAZ40509.1
DQ117584 mRNA Translation: AAZ40510.1
DQ117585 mRNA Translation: AAZ40511.1
DQ117586 mRNA Translation: AAZ40512.1
DQ117587 mRNA Translation: AAZ40513.1
DQ117588 mRNA Translation: AAZ40514.1
DQ117589 mRNA Translation: AAZ40515.1
DQ117590 mRNA Translation: AAZ40516.1

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ117583 mRNA Translation: AAZ40509.1
DQ117584 mRNA Translation: AAZ40510.1
DQ117585 mRNA Translation: AAZ40511.1
DQ117586 mRNA Translation: AAZ40512.1
DQ117587 mRNA Translation: AAZ40513.1
DQ117588 mRNA Translation: AAZ40514.1
DQ117589 mRNA Translation: AAZ40515.1
DQ117590 mRNA Translation: AAZ40516.1

3D structure databases

SMRiQ2LKW6
ModBaseiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-4261, NLRP1b inflammasome, allele-1 variant
IntActiQ2LKW6, 1 interactor

Proteomic databases

PRIDEiQ2LKW6

Organism-specific databases

MGIiMGI:3582959, Nlrp1b

Miscellaneous databases

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Family and domain databases

CDDicd08330, CARD_ASC_NALP1, 1 hit
Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR001315, CARD
IPR033516, CARD8/ASC/NALP1_CARD
IPR011029, DEATH-like_dom_sf
IPR025307, FIIND_dom
IPR032675, LRR_dom_sf
IPR007111, NACHT_NTPase
IPR041267, NLRP_HD2
IPR041075, NOD2_WH
IPR027417, P-loop_NTPase
PfamiView protein in Pfam
PF00619, CARD, 1 hit
PF13553, FIIND, 1 hit
PF05729, NACHT, 1 hit
PF17776, NLRC4_HD2, 1 hit
PF17779, NOD2_WH, 1 hit
SUPFAMiSSF47986, SSF47986, 1 hit
SSF52540, SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50209, CARD, 1 hit
PS51830, FIIND, 1 hit
PS51450, LRR, 2 hits
PS50837, NACHT, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiNL1B1_MOUSE
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q2LKW6
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 9, 2015
Last sequence update: February 21, 2006
Last modified: June 2, 2021
This is version 97 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families
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