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Q8R4B8

- NALP3_MOUSE

UniProt

Q8R4B8 - NALP3_MOUSE

Protein

NACHT, LRR and PYD domains-containing protein 3

Gene

Nlrp3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    Functioni

    May function as an inducer of apoptosis. Interacts selectively with ASC and this complex may function as an upstream activator of NF-kappa-B signaling. Inhibits TNF-alpha induced activation and nuclear translocation of RELA/NF-KB p65. Also inhibits transcriptional activity of RELA By similarity. Activates caspase-1 as part of the NALP3 inflammasome complex in response to a number of triggers including bacterial or viral infection which leads to processing and release of IL1B and IL18.By similarity4 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi222 – 2298ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
    2. cellular response to lipopolysaccharide Source: Ensembl
    3. defense response to virus Source: MGI
    4. inflammatory response Source: HGNC
    5. interleukin-18 production Source: MGI
    6. interleukin-1 beta production Source: MGI
    7. interleukin-1 secretion Source: MGI
    8. negative regulation of acute inflammatory response Source: Ensembl
    9. negative regulation of interleukin-1 beta secretion Source: Ensembl
    10. negative regulation of NF-kappaB import into nucleus Source: HGNC
    11. negative regulation of NF-kappaB transcription factor activity Source: HGNC
    12. NLRP3 inflammasome complex assembly Source: MGI
    13. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: HGNC
    14. positive regulation of interleukin-1 beta secretion Source: HGNC
    15. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
    16. regulation of inflammatory response Source: MGI

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_198644. The NLRP3 inflammasome.

    Names & Taxonomyi

    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
    Gene namesi
    Name:Nlrp3
    Synonyms:Cias1, Mmig1, Nalp3, Pypaf1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:2653833. Nlrp3.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. NLRP3 inflammasome complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Mice display lack of activation of caspase-1 in response to stimuli such as LPS and ATP, viral infection, bacterial and viral RNA, non-viral double-stranded RNA, nigericin, maitotoxin and the imidazoquinoline compounds R837 and R848.4 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10331033NACHT, LRR and PYD domains-containing protein 3PRO_0000080887Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi6 ↔ 104Redox-activeBy similarity

    Post-translational modificationi

    The disulfide bond in the DAPIN domain may play a role in inflammation activation by reactive oxygen species.By similarity

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiQ8R4B8.
    PRIDEiQ8R4B8.

    PTM databases

    PhosphoSiteiQ8R4B8.

    Expressioni

    Tissue specificityi

    Widely expressed with high levels in peripheral blood leukocytes. Not detected in thymus.2 Publications

    Gene expression databases

    ArrayExpressiQ8R4B8.
    BgeeiQ8R4B8.
    CleanExiMM_NLRP3.
    GenevestigatoriQ8R4B8.

    Interactioni

    Subunit structurei

    Part of the NALP3 inflammasome complex which is involved in activation of caspase-1 and caspase-5, leading to processing of IL1B and IL18. Interacts with PYCARD/ASC, PML (isoform PML-1), EIF2AK2/PKR and MEFV By similarity.By similarity

    Protein-protein interaction databases

    DIPiDIP-60132N.
    IntActiQ8R4B8. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8R4B8.
    SMRiQ8R4B8. Positions 3-92.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 9191DAPINPROSITE-ProRule annotationAdd
    BLAST
    Domaini216 – 532317NACHTPROSITE-ProRule annotationAdd
    BLAST
    Repeati739 – 75921LRR 1Add
    BLAST
    Repeati768 – 78922LRR 2Add
    BLAST
    Repeati796 – 81621LRR 3Add
    BLAST
    Repeati825 – 84622LRR 4Add
    BLAST
    Repeati853 – 87321LRR 5Add
    BLAST
    Repeati882 – 90322LRR 6Add
    BLAST
    Repeati910 – 93021LRR 7Add
    BLAST
    Repeati939 – 96022LRR 8Add
    BLAST
    Repeati967 – 98822LRR 9Add
    BLAST

    Sequence similaritiesi

    Belongs to the NLRP family.Curated
    Contains 1 DAPIN domain.PROSITE-ProRule annotation
    Contains 9 LRR (leucine-rich) repeats.Curated
    Contains 1 NACHT domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Leucine-rich repeat, Repeat

    Phylogenomic databases

    eggNOGiNOG82860.
    GeneTreeiENSGT00740000115159.
    HOGENOMiHOG000294064.
    HOVERGENiHBG063656.
    InParanoidiQ8R4B8.
    KOiK12800.
    OMAiSKQEREH.
    OrthoDBiEOG7P5T07.
    PhylomeDBiQ8R4B8.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    InterProiIPR004020. DAPIN.
    IPR011029. DEATH-like_dom.
    IPR001611. Leu-rich_rpt.
    IPR003590. Leu-rich_rpt_RNase_inh_sub-typ.
    IPR007111. NACHT_NTPase.
    IPR029495. NATCH-assoc.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF14484. FISNA. 1 hit.
    PF02758. PYRIN. 1 hit.
    [Graphical view]
    SMARTiSM00368. LRR_RI. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    SSF52540. SSF52540. 2 hits.
    PROSITEiPS50824. DAPIN. 1 hit.
    PS51450. LRR. 5 hits.
    PS50837. NACHT. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8R4B8-1) [UniParc]FASTAAdd to Basket

    Also known as: MMIG-1a

    This isoform has been chosen as the 'canonical' 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

    MTSVRCKLAQ YLEDLEDVDL KKFKMHLEDY PPEKGCIPVP RGQMEKADHL     50
    DLATLMIDFN GEEKAWAMAV WIFAAINRRD LWEKAKKDQP EWNDTCTSHS 100
    SMVCQEDSLE EEWMGLLGYL SRISICKKKK DYCKMYRRHV RSRFYSIKDR 150
    NARLGESVDL NSRYTQLQLV KEHPSKQERE HELLTIGRTK MRDSPMSSLK 200
    LELLFEPEDG HSEPVHTVVF QGAAGIGKTI LARKIMLDWA LGKLFKDKFD 250
    YLFFIHCREV SLRTPRSLAD LIVSCWPDPN PPVCKILRKP SRILFLMDGF 300
    DELQGAFDEH IGEVCTDWQK AVRGDILLSS LIRKKLLPKA SLLITTRPVA 350
    LEKLQHLLDH PRHVEILGFS EAKRKEYFFK YFSNELQARE AFRLIQENEV 400
    LFTMCFIPLV CWIVCTGLKQ QMETGKSLAQ TSKTTTAVYV FFLSSLLQSR 450
    GGIEEHLFSD YLQGLCSLAA DGIWNQKILF EECDLRKHGL QKTDVSAFLR 500
    MNVFQKEVDC ERFYSFSHMT FQEFFAAMYY LLEEEAEGET VRKGPGGCSD 550
    LLNRDVKVLL ENYGKFEKGY LIFVVRFLFG LVNQERTSYL EKKLSCKISQ 600
    QVRLELLKWI EVKAKAKKLQ WQPSQLELFY CLYEMQEEDF VQSAMDHFPK 650
    IEINLSTRMD HVVSSFCIKN CHRVKTLSLG FFHNSPKEEE EERRGGRPLD 700
    QVQCVFPDTH VACSSRLVNC CLTSSFCRGL FSSLSTNRSL TELDLSDNTL 750
    GDPGMRVLCE ALQHPGCNIQ RLWLGRCGLS HQCCFDISSV LSSSQKLVEL 800
    DLSDNALGDF GIRLLCVGLK HLLCNLQKLW LVSCCLTSAC CQDLALVLSS 850
    NHSLTRLYIG ENALGDSGVQ VLCEKMKDPQ CNLQKLGLVN SGLTSICCSA 900
    LTSVLKTNQN FTHLYLRSNA LGDTGLRLLC EGLLHPDCKL QMLELDNCSL 950
    TSHSCWNLST ILTHNHSLRK LNLGNNDLGD LCVVTLCEVL KQQGCLLQSL 1000
    QLGEMYLNRE TKRALEALQE EKPELTIVFE ISW 1033
    Length:1,033
    Mass (Da):118,275
    Last modified:June 1, 2002 - v1
    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

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei774 – 83057Missing in isoform 3. 1 PublicationVSP_014925Add
    BLAST
    Alternative sequencei830 – 1033204Missing in isoform 4. 2 PublicationsVSP_014926Add
    BLAST
    Alternative sequencei888 – 94457Missing in isoform 2. 1 PublicationVSP_014927Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF486632 mRNA. Translation: AAL90874.1.
    AY495376 mRNA. Translation: AAS75794.1.
    AY495377 mRNA. Translation: AAS75795.1.
    AY337285 mRNA. Translation: AAR03540.1.
    AY337292
    , AY337286, AY337287, AY337288, AY337289, AY337290, AY337291 Genomic DNA. Translation: AAR03541.1.
    AY337299
    , AY337293, AY337294, AY337295, AY337296, AY337297, AY337298 Genomic DNA. Translation: AAR03542.1.
    AY337306
    , AY337300, AY337301, AY337302, AY337303, AY337304, AY337305 Genomic DNA. Translation: AAR03543.1.
    AY355340 mRNA. Translation: AAR14737.1.
    AL592522 Genomic DNA. Translation: CAI24551.1.
    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. [Q8R4B8-1]
    XP_006532921.1. XM_006532858.1. [Q8R4B8-1]
    XP_006532922.1. XM_006532859.1. [Q8R4B8-1]
    UniGeneiMm.54174.

    Genome annotation databases

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

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF486632 mRNA. Translation: AAL90874.1 .
    AY495376 mRNA. Translation: AAS75794.1 .
    AY495377 mRNA. Translation: AAS75795.1 .
    AY337285 mRNA. Translation: AAR03540.1 .
    AY337292
    , AY337286 , AY337287 , AY337288 , AY337289 , AY337290 , AY337291 Genomic DNA. Translation: AAR03541.1 .
    AY337299
    , AY337293 , AY337294 , AY337295 , AY337296 , AY337297 , AY337298 Genomic DNA. Translation: AAR03542.1 .
    AY337306
    , AY337300 , AY337301 , AY337302 , AY337303 , AY337304 , AY337305 Genomic DNA. Translation: AAR03543.1 .
    AY355340 mRNA. Translation: AAR14737.1 .
    AL592522 Genomic DNA. Translation: CAI24551.1 .
    BC116174 mRNA. Translation: AAI16175.1 .
    BC116175 mRNA. Translation: AAI16176.1 .
    CCDSi CCDS24771.1. [Q8R4B8-1 ]
    RefSeqi NP_665826.1. NM_145827.3. [Q8R4B8-1 ]
    XP_006532920.1. XM_006532857.1. [Q8R4B8-1 ]
    XP_006532921.1. XM_006532858.1. [Q8R4B8-1 ]
    XP_006532922.1. XM_006532859.1. [Q8R4B8-1 ]
    UniGenei Mm.54174.

    3D structure databases

    ProteinModelPortali Q8R4B8.
    SMRi Q8R4B8. Positions 3-92.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-60132N.
    IntActi Q8R4B8. 1 interaction.

    PTM databases

    PhosphoSitei Q8R4B8.

    Proteomic databases

    PaxDbi Q8R4B8.
    PRIDEi Q8R4B8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000079476 ; ENSMUSP00000078440 ; ENSMUSG00000032691 . [Q8R4B8-1 ]
    ENSMUST00000101148 ; ENSMUSP00000098707 ; ENSMUSG00000032691 . [Q8R4B8-1 ]
    GeneIDi 216799.
    KEGGi mmu:216799.
    UCSCi uc007jeh.1. mouse. [Q8R4B8-1 ]

    Organism-specific databases

    CTDi 114548.
    MGIi MGI:2653833. Nlrp3.

    Phylogenomic databases

    eggNOGi NOG82860.
    GeneTreei ENSGT00740000115159.
    HOGENOMi HOG000294064.
    HOVERGENi HBG063656.
    InParanoidi Q8R4B8.
    KOi K12800.
    OMAi SKQEREH.
    OrthoDBi EOG7P5T07.
    PhylomeDBi Q8R4B8.

    Enzyme and pathway databases

    Reactomei REACT_198644. The NLRP3 inflammasome.

    Miscellaneous databases

    NextBioi 375328.
    PROi Q8R4B8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8R4B8.
    Bgeei Q8R4B8.
    CleanExi MM_NLRP3.
    Genevestigatori Q8R4B8.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    InterProi IPR004020. DAPIN.
    IPR011029. DEATH-like_dom.
    IPR001611. Leu-rich_rpt.
    IPR003590. Leu-rich_rpt_RNase_inh_sub-typ.
    IPR007111. NACHT_NTPase.
    IPR029495. NATCH-assoc.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    Pfami PF14484. FISNA. 1 hit.
    PF02758. PYRIN. 1 hit.
    [Graphical view ]
    SMARTi SM00368. LRR_RI. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    SSF52540. SSF52540. 2 hits.
    PROSITEi PS50824. DAPIN. 1 hit.
    PS51450. LRR. 5 hits.
    PS50837. NACHT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), SUBCELLULAR LOCATION.
      Strain: BALB/cJ.
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
      Strain: 129/Sv, BALB/c and C57BL/6.
    3. "Murine NALPs: a family of proteins involved in inflammation."
      Martinon F., Hofmann K., Tschopp J.
      Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Strain: C57BL/6.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
    6. "Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1."
      Sutterwala F.S., Ogura Y., Szczepanik M., Lara-Tejero M., Lichtenberger G.S., Grant E.P., Bertin J., Coyle A.J., Galan J.E., Askenase P.W., Flavell R.A.
      Immunity 24:317-327(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
    7. "Critical role for cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA."
      Kanneganti T.-D., Body-Malapel M., Amer A., Park J.-H., Whitfield J., Franchi L., Taraporewala Z.F., Miller D., Patton J.T., Inohara N., Nunez G.
      J. Biol. Chem. 281:36560-36568(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    8. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    9. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    10. Cited for: INTERACTION WITH EIF2AK2.

    Entry informationi

    Entry nameiNALP3_MOUSE
    AccessioniPrimary (citable) accession number: Q8R4B8
    Secondary accession number(s): Q1JQ87, Q1JQ88, Q6JEL0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 28, 2003
    Last sequence update: June 1, 2002
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Expression is increased in mice with experimental atopic dermatitis.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3