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Entry version 171 (17 Jun 2020)
Sequence version 1 (01 Jun 2002)
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Protein

NACHT, LRR and PYD domains-containing protein 3

Gene

Nlrp3

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

As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (or possibly CASP4/CASP11). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu (PubMed:28847925, PubMed:27374331). Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K+ efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33 (By similarity). Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth. During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (PubMed:26098997).By similarity8 Publications

Miscellaneous

Expression is increased in mice with experimental atopic dermatitis.

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 bindingi222 – 229ATPPROSITE-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 functionActivator
Biological processImmunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-5689901 Metalloprotease DUBs
R-MMU-844456 The NLRP3 inflammasome

<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 3
Alternative name(s):
Cold autoinflammatory syndrome 1 protein homolog
Cryopyrin
Mast cell maturation-associated-inducible protein 1
PYRIN-containing APAF1-like protein 1
<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:Nlrp3
Synonyms:Cias1, Mmig1, Nalp3, Pypaf1
<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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

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

More...
MGIi
MGI:2653833 Nlrp3

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Inflammasome, Nucleus, Secreted

<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

Knockout mice are fertile and appear healthy when housed in a standard specific pathogen-free environment. They do not exhibit any increase in serum IL1B after administration of R837 (an analog to guanosine and TLR7 agonist) and/or LPS (PubMed:16407890) (PubMed:16407888). When challenged with LPS, mutant mice are partially resistant to endotoxic shock (PubMed:16546100) (PubMed:16407890). Mutant mice display impaired contact hypersensitivity, a T-cell-mediated cellular immune response to repeated epicutaneous exposure to contact allergens, such as trinitrophenylchloride (PubMed:16546100). In a model of allergic asthma that promotes strictly Th2 responses, mutant animals show less infiltration of eosinophils and lymphocytes into the lungs than their wild-type counterparts, as well as less accumulation of mucus and lymphoid infiltrates. The concentration of Th2 cell-related cytokines, including IL-5 and IL-4, is also lower in lungs from mutant mice compared to wild-type (PubMed:26098997). Knockout mice develop insulin (INS) resistance in response to high-fat diet.5 Publications

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL3779755

<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_00000808871 – 1033NACHT, LRR and PYD domains-containing protein 3Add BLAST1033

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi6 ↔ 104Redox-activeBy similarity

<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

Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Ubiquitination does not lead to degradation, but inhibits inflammasome activation (PubMed:23246432). Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 activation and inflammasome assembly. This process can be induced by the activation of Toll-like receptors (by LPS), through a non-transcriptional pathway dependent on the mitochondrial production of reactive oxygen species, and by ATP.2 Publications
The disulfide bond in the pyrin domain might play a role in reactive oxygen species-mediated activation.By similarity

Keywords - PTMi

Disulfide bond, Ubl conjugation

Proteomic databases

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
Q8R4B8

PRoteomics IDEntifications database

More...
PRIDEi
Q8R4B8

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
Q8R4B8

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
Q8R4B8

<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

Expressed with high levels in peripheral blood leukocytes, including Th2 lymphocytes and macrophages (PubMed:15302403, PubMed:26098997, PubMed:16546100, PubMed:28847925). Expressed at low levels in resting osteoblasts (at protein level) (PubMed:17907925).5 Publications

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Up-regulated during CD4+ T-lymphocyte differentiation, in Th0, Th1 and Th2 cells. Not detected in naive CD4+ T-lymphocytes (at protein level).2 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

By activators of Toll-like receptors, such as lipoteichoic acid (LTA) (TLR2), polyinosine-polycytidylic acid (poly(I:C), a synthetic analog of dsRNA) (TLR3) and bacterial lipopolysaccharides (LPS) (TLR4) (PubMed:16546100). Up-regulated by IL2 via STAT5 signaling (PubMed:26098997). Slightly up-regulated in osteoblasts after exposure to invasive, but not invasion-defective, strains of Salmonella typhimurium (at protein level) (PubMed:17907925).3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSMUSG00000032691 Expressed in spinal cord and 61 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q8R4B8 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q8R4B8 MM

<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

Sensor component of NLRP3 inflammasomes. 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. The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (ASC/PYCARD), which recruits an effector proinflammatory caspase (CASP1 and, possibly, CASP4 and CASP5). Within the complex, NLRP3 and PYCARD interact via their respective pyrin domains. This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process. NLRP3 localizes at the end of each PYCARD filament. Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization. CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. Reconstituted ternary inflammasomes show star-shaped structures, in which multiple filaments, containing CASP1, protrude radially from a single central hub, containing the sensor protein and PYCARD. In this complex, the sensor protein is sub-stoichiometric to PYCARD, and PYCARD is further substoichiometric to CASP1, suggesting amplifications of signal transduction from the sensor, via the adapter, to the effector (By similarity).

Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity).

Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (By similarity).

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

Interacts with PML (isoform PML-1) (via the LRR region); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction. Directly interacts with IRF4 (via LRR region); this interaction is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T-cells (PubMed:26098997).

Interacts (via NACHT domain) with DHX33 (via DEAH box) (By similarity).

Interacts with PYDC5 (By similarity).

Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions (PubMed:31511697).

Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by omega-3 polyunsaturated fatty acids (PUFAs).

By similarity3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
229789, 1 interactor

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-4241 NLRP3 inflammasome

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q8R4B8

Database of interacting proteins

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DIPi
DIP-60132N

Protein interaction database and analysis system

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IntActi
Q8R4B8, 5 interactors

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000098707

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q8R4B8

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
Q8R4B8 protein

<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
Q8R4B8

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>Domaini1 – 91PyrinPROSITE-ProRule annotationAdd BLAST91
Domaini216 – 532NACHTPROSITE-ProRule annotationAdd BLAST317
<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>Repeati739 – 759LRR 1Add BLAST21
Repeati768 – 789LRR 2Add BLAST22
Repeati796 – 816LRR 3Add BLAST21
Repeati825 – 846LRR 4Add BLAST22
Repeati853 – 873LRR 5Add BLAST21
Repeati882 – 903LRR 6Add BLAST22
Repeati910 – 930LRR 7Add BLAST21
Repeati939 – 960LRR 8Add BLAST22
Repeati967 – 988LRR 9Add BLAST22

<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 LRR domain mediates the interaction with IRF4 and PML.By similarity1 Publication
Intramolecular interactions between NACHT and leucine-rich repeat (LRR) domains may be important for autoinhibition in the absence of activating signal.By similarity
The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD-binding.

<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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IE5X Eukaryota
ENOG4111H3D LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000162415

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_002274_2_0_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q8R4B8

KEGG Orthology (KO)

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KOi
K12800

Identification of Orthologs from Complete Genome Data

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OMAi
FHCIEDR

Database of Orthologous Groups

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OrthoDBi
114368at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q8R4B8

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.80.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR029495 NACHT-assoc
IPR007111 NACHT_NTPase
IPR041267 NLRC_HD2
IPR041075 NOD2_WH
IPR027417 P-loop_NTPase

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF14484 FISNA, 1 hit
PF13516 LRR_6, 5 hits
PF05729 NACHT, 1 hit
PF17776 NLRC4_HD2, 1 hit
PF17779 NOD2_WH, 1 hit
PF02758 PYRIN, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM01288 FISNA, 1 hit
SM01289 PYRIN, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF47986 SSF47986, 1 hit
SSF52540 SSF52540, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50824 DAPIN, 1 hit
PS51450 LRR, 5 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>Sequences (4+)i

<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.

This entry describes 4 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q8R4B8-1) [UniParc]FASTAAdd to basket
Also known as: MMIG-1a

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MTSVRCKLAQ YLEDLEDVDL KKFKMHLEDY PPEKGCIPVP RGQMEKADHL
60 70 80 90 100
DLATLMIDFN GEEKAWAMAV WIFAAINRRD LWEKAKKDQP EWNDTCTSHS
110 120 130 140 150
SMVCQEDSLE EEWMGLLGYL SRISICKKKK DYCKMYRRHV RSRFYSIKDR
160 170 180 190 200
NARLGESVDL NSRYTQLQLV KEHPSKQERE HELLTIGRTK MRDSPMSSLK
210 220 230 240 250
LELLFEPEDG HSEPVHTVVF QGAAGIGKTI LARKIMLDWA LGKLFKDKFD
260 270 280 290 300
YLFFIHCREV SLRTPRSLAD LIVSCWPDPN PPVCKILRKP SRILFLMDGF
310 320 330 340 350
DELQGAFDEH IGEVCTDWQK AVRGDILLSS LIRKKLLPKA SLLITTRPVA
360 370 380 390 400
LEKLQHLLDH PRHVEILGFS EAKRKEYFFK YFSNELQARE AFRLIQENEV
410 420 430 440 450
LFTMCFIPLV CWIVCTGLKQ QMETGKSLAQ TSKTTTAVYV FFLSSLLQSR
460 470 480 490 500
GGIEEHLFSD YLQGLCSLAA DGIWNQKILF EECDLRKHGL QKTDVSAFLR
510 520 530 540 550
MNVFQKEVDC ERFYSFSHMT FQEFFAAMYY LLEEEAEGET VRKGPGGCSD
560 570 580 590 600
LLNRDVKVLL ENYGKFEKGY LIFVVRFLFG LVNQERTSYL EKKLSCKISQ
610 620 630 640 650
QVRLELLKWI EVKAKAKKLQ WQPSQLELFY CLYEMQEEDF VQSAMDHFPK
660 670 680 690 700
IEINLSTRMD HVVSSFCIKN CHRVKTLSLG FFHNSPKEEE EERRGGRPLD
710 720 730 740 750
QVQCVFPDTH VACSSRLVNC CLTSSFCRGL FSSLSTNRSL TELDLSDNTL
760 770 780 790 800
GDPGMRVLCE ALQHPGCNIQ RLWLGRCGLS HQCCFDISSV LSSSQKLVEL
810 820 830 840 850
DLSDNALGDF GIRLLCVGLK HLLCNLQKLW LVSCCLTSAC CQDLALVLSS
860 870 880 890 900
NHSLTRLYIG ENALGDSGVQ VLCEKMKDPQ CNLQKLGLVN SGLTSICCSA
910 920 930 940 950
LTSVLKTNQN FTHLYLRSNA LGDTGLRLLC EGLLHPDCKL QMLELDNCSL
960 970 980 990 1000
TSHSCWNLST ILTHNHSLRK LNLGNNDLGD LCVVTLCEVL KQQGCLLQSL
1010 1020 1030
QLGEMYLNRE TKRALEALQE EKPELTIVFE ISW
Length:1,033
Mass (Da):118,275
Last modified:June 1, 2002 - 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:i5924690966B12117
GO
Isoform 2 (identifier: Q8R4B8-2) [UniParc]FASTAAdd to basket
Also known as: MMIG-1b

The sequence of this isoform differs from the canonical sequence as follows:
     888-944: Missing.

Show »
Length:976
Mass (Da):112,073
Checksum:i01C3B9AC1D01C9D8
GO
Isoform 3 (identifier: Q8R4B8-3) [UniParc]FASTAAdd to basket
Also known as: MMIG-1c

The sequence of this isoform differs from the canonical sequence as follows:
     774-830: Missing.

Show »
Length:976
Mass (Da):112,032
Checksum:iC8D9FB1ECD871D5E
GO
Isoform 4 (identifier: Q8R4B8-4) [UniParc]FASTAAdd to basket
Also known as: MMIG-1d

The sequence of this isoform differs from the canonical sequence as follows:
     830-1033: Missing.

Show »
Length:829
Mass (Da):95,710
Checksum:i9F8A2ABC9CAE7004
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SXI6Q5SXI6_MOUSE
NACHT, LRR and PYD domains-containi...
Nlrp3
173Annotation score:

Annotation score:1 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 Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti491Q → R in AGU01502 (Ref. 4) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_014925774 – 830Missing in isoform 3. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_014926830 – 1033Missing in isoform 4. 2 PublicationsAdd BLAST204
Alternative sequenceiVSP_014927888 – 944Missing in isoform 2. 1 PublicationAdd BLAST57

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
AF486632 mRNA Translation: AAL90874.1
AY495376 mRNA Translation: AAS75794.1
AY495377 mRNA Translation: AAS75795.1
AY337285 mRNA Translation: AAR03540.1
AY337292 AY337291 Genomic DNA Translation: AAR03541.1
AY337299 AY337298 Genomic DNA Translation: AAR03542.1
AY337306 AY337305 Genomic DNA Translation: AAR03543.1
AY355340 mRNA Translation: AAR14737.1
KF032621 mRNA Translation: AGU01502.1
AL592522 Genomic DNA No translation available.
BC116174 mRNA Translation: AAI16175.1
BC116175 mRNA Translation: AAI16176.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS24771.1 [Q8R4B8-1]

NCBI Reference Sequences

More...
RefSeqi
NP_665826.1, NM_145827.3 [Q8R4B8-1]
XP_006532920.1, XM_006532857.1
XP_006532921.1, XM_006532858.1 [Q8R4B8-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENSMUST00000079476; ENSMUSP00000078440; ENSMUSG00000032691 [Q8R4B8-1]
ENSMUST00000101148; ENSMUSP00000098707; ENSMUSG00000032691 [Q8R4B8-1]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
216799

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
mmu:216799

UCSC genome browser

More...
UCSCi
uc007jeh.1 mouse [Q8R4B8-1]

Keywords - Coding sequence diversityi

Alternative splicing

<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
AF486632 mRNA Translation: AAL90874.1
AY495376 mRNA Translation: AAS75794.1
AY495377 mRNA Translation: AAS75795.1
AY337285 mRNA Translation: AAR03540.1
AY337292 AY337291 Genomic DNA Translation: AAR03541.1
AY337299 AY337298 Genomic DNA Translation: AAR03542.1
AY337306 AY337305 Genomic DNA Translation: AAR03543.1
AY355340 mRNA Translation: AAR14737.1
KF032621 mRNA Translation: AGU01502.1
AL592522 Genomic DNA No translation available.
BC116174 mRNA Translation: AAI16175.1
BC116175 mRNA Translation: AAI16176.1
CCDSiCCDS24771.1 [Q8R4B8-1]
RefSeqiNP_665826.1, NM_145827.3 [Q8R4B8-1]
XP_006532920.1, XM_006532857.1
XP_006532921.1, XM_006532858.1 [Q8R4B8-1]

3D structure databases

SMRiQ8R4B8
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi229789, 1 interactor
ComplexPortaliCPX-4241 NLRP3 inflammasome
CORUMiQ8R4B8
DIPiDIP-60132N
IntActiQ8R4B8, 5 interactors
STRINGi10090.ENSMUSP00000098707

Chemistry databases

BindingDBiQ8R4B8
ChEMBLiCHEMBL3779755

PTM databases

iPTMnetiQ8R4B8
PhosphoSitePlusiQ8R4B8

Proteomic databases

PaxDbiQ8R4B8
PRIDEiQ8R4B8

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
624 760 antibodies

Genome annotation databases

EnsembliENSMUST00000079476; ENSMUSP00000078440; ENSMUSG00000032691 [Q8R4B8-1]
ENSMUST00000101148; ENSMUSP00000098707; ENSMUSG00000032691 [Q8R4B8-1]
GeneIDi216799
KEGGimmu:216799
UCSCiuc007jeh.1 mouse [Q8R4B8-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
114548
MGIiMGI:2653833 Nlrp3

Phylogenomic databases

eggNOGiENOG410IE5X Eukaryota
ENOG4111H3D LUCA
GeneTreeiENSGT00940000162415
HOGENOMiCLU_002274_2_0_1
InParanoidiQ8R4B8
KOiK12800
OMAiFHCIEDR
OrthoDBi114368at2759
PhylomeDBiQ8R4B8

Enzyme and pathway databases

ReactomeiR-MMU-5689901 Metalloprotease DUBs
R-MMU-844456 The NLRP3 inflammasome

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
216799 0 hits in 12 CRISPR screens

Protein Ontology

More...
PROi
PR:Q8R4B8
RNActiQ8R4B8 protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000032691 Expressed in spinal cord and 61 other tissues
ExpressionAtlasiQ8R4B8 baseline and differential
GenevisibleiQ8R4B8 MM

Family and domain databases

Gene3Di3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
IPR001611 Leu-rich_rpt
IPR032675 LRR_dom_sf
IPR029495 NACHT-assoc
IPR007111 NACHT_NTPase
IPR041267 NLRC_HD2
IPR041075 NOD2_WH
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF14484 FISNA, 1 hit
PF13516 LRR_6, 5 hits
PF05729 NACHT, 1 hit
PF17776 NLRC4_HD2, 1 hit
PF17779 NOD2_WH, 1 hit
PF02758 PYRIN, 1 hit
SMARTiView protein in SMART
SM01288 FISNA, 1 hit
SM01289 PYRIN, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS50824 DAPIN, 1 hit
PS51450 LRR, 5 hits
PS50837 NACHT, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

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 nameiNLRP3_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: Q8R4B8
Secondary accession number(s): Q1JQ87
, Q1JQ88, Q6JEL0, T1W2H6
<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: March 28, 2003
Last sequence update: June 1, 2002
Last modified: June 17, 2020
This is version 171 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

Keywords - Technical termi

Reference proteome

Documents

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