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Q8R4B8 (NALP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Nlrp3
Synonyms:Cias1, Mmig1, Nalp3, Pypaf1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1033 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

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. Ref.10

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Widely expressed with high levels in peripheral blood leukocytes. Not detected in thymus. Ref.2 Ref.6

Post-translational modification

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

Disruption phenotype

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. Ref.6 Ref.7 Ref.8 Ref.9

Miscellaneous

Expression is increased in mice with experimental atopic dermatitis.

Sequence similarities

Belongs to the NLRP family.

Contains 1 DAPIN domain.

Contains 9 LRR (leucine-rich) repeats.

Contains 1 NACHT domain.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainLeucine-rich repeat
Repeat
   LigandATP-binding
Nucleotide-binding
   PTMDisulfide bond
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNLRP3 inflammasome complex assembly

Inferred from mutant phenotype PubMed 22753929. Source: MGI

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype Ref.7. Source: MGI

cellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from mutant phenotype Ref.7. Source: MGI

inflammatory response

Inferred from sequence or structural similarity. Source: HGNC

interleukin-1 beta production

Inferred from mutant phenotype PubMed 22753929. Source: MGI

interleukin-1 secretion

Inferred from mutant phenotype Ref.7. Source: MGI

interleukin-18 production

Inferred from mutant phenotype Ref.7. Source: MGI

negative regulation of NF-kappaB import into nucleus

Inferred from sequence or structural similarity. Source: HGNC

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: HGNC

negative regulation of acute inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-1 beta secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of interleukin-1 beta secretion

Inferred from sequence or structural similarity. Source: HGNC

regulation of inflammatory response

Inferred from mutant phenotype PubMed 22297845. Source: MGI

   Cellular_componentNLRP3 inflammasome complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8R4B8-1)

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.
Isoform 2 (identifier: Q8R4B8-2)

Also known as: MMIG-1b;

The sequence of this isoform differs from the canonical sequence as follows:
     888-944: Missing.
Isoform 3 (identifier: Q8R4B8-3)

Also known as: MMIG-1c;

The sequence of this isoform differs from the canonical sequence as follows:
     774-830: Missing.
Isoform 4 (identifier: Q8R4B8-4)

Also known as: MMIG-1d;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10331033NACHT, LRR and PYD domains-containing protein 3
PRO_0000080887

Regions

Domain1 – 9191DAPIN
Domain216 – 532317NACHT
Repeat739 – 75921LRR 1
Repeat768 – 78922LRR 2
Repeat796 – 81621LRR 3
Repeat825 – 84622LRR 4
Repeat853 – 87321LRR 5
Repeat882 – 90322LRR 6
Repeat910 – 93021LRR 7
Repeat939 – 96022LRR 8
Repeat967 – 98822LRR 9
Nucleotide binding222 – 2298ATP Potential

Amino acid modifications

Disulfide bond6 ↔ 104Redox-active By similarity

Natural variations

Alternative sequence774 – 83057Missing in isoform 3.
VSP_014925
Alternative sequence830 – 1033204Missing in isoform 4.
VSP_014926
Alternative sequence888 – 94457Missing in isoform 2.
VSP_014927

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MMIG-1a) [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: 5924690966B12117

FASTA1,033118,275
        10         20         30         40         50         60 
MTSVRCKLAQ YLEDLEDVDL KKFKMHLEDY PPEKGCIPVP RGQMEKADHL DLATLMIDFN 

        70         80         90        100        110        120 
GEEKAWAMAV WIFAAINRRD LWEKAKKDQP EWNDTCTSHS SMVCQEDSLE EEWMGLLGYL 

       130        140        150        160        170        180 
SRISICKKKK DYCKMYRRHV RSRFYSIKDR NARLGESVDL NSRYTQLQLV KEHPSKQERE 

       190        200        210        220        230        240 
HELLTIGRTK MRDSPMSSLK LELLFEPEDG HSEPVHTVVF QGAAGIGKTI LARKIMLDWA 

       250        260        270        280        290        300 
LGKLFKDKFD YLFFIHCREV SLRTPRSLAD LIVSCWPDPN PPVCKILRKP SRILFLMDGF 

       310        320        330        340        350        360 
DELQGAFDEH IGEVCTDWQK AVRGDILLSS LIRKKLLPKA SLLITTRPVA LEKLQHLLDH 

       370        380        390        400        410        420 
PRHVEILGFS EAKRKEYFFK YFSNELQARE AFRLIQENEV LFTMCFIPLV CWIVCTGLKQ 

       430        440        450        460        470        480 
QMETGKSLAQ TSKTTTAVYV FFLSSLLQSR GGIEEHLFSD YLQGLCSLAA DGIWNQKILF 

       490        500        510        520        530        540 
EECDLRKHGL QKTDVSAFLR MNVFQKEVDC ERFYSFSHMT FQEFFAAMYY LLEEEAEGET 

       550        560        570        580        590        600 
VRKGPGGCSD LLNRDVKVLL ENYGKFEKGY LIFVVRFLFG LVNQERTSYL EKKLSCKISQ 

       610        620        630        640        650        660 
QVRLELLKWI EVKAKAKKLQ WQPSQLELFY CLYEMQEEDF VQSAMDHFPK IEINLSTRMD 

       670        680        690        700        710        720 
HVVSSFCIKN CHRVKTLSLG FFHNSPKEEE EERRGGRPLD QVQCVFPDTH VACSSRLVNC 

       730        740        750        760        770        780 
CLTSSFCRGL FSSLSTNRSL TELDLSDNTL GDPGMRVLCE ALQHPGCNIQ RLWLGRCGLS 

       790        800        810        820        830        840 
HQCCFDISSV LSSSQKLVEL DLSDNALGDF GIRLLCVGLK HLLCNLQKLW LVSCCLTSAC 

       850        860        870        880        890        900 
CQDLALVLSS NHSLTRLYIG ENALGDSGVQ VLCEKMKDPQ CNLQKLGLVN SGLTSICCSA 

       910        920        930        940        950        960 
LTSVLKTNQN FTHLYLRSNA LGDTGLRLLC EGLLHPDCKL QMLELDNCSL TSHSCWNLST 

       970        980        990       1000       1010       1020 
ILTHNHSLRK LNLGNNDLGD LCVVTLCEVL KQQGCLLQSL QLGEMYLNRE TKRALEALQE 

      1030 
EKPELTIVFE ISW 

« Hide

Isoform 2 (MMIG-1b) [UniParc].

Checksum: 01C3B9AC1D01C9D8
Show »

FASTA976112,073
Isoform 3 (MMIG-1c) [UniParc].

Checksum: C8D9FB1ECD871D5E
Show »

FASTA976112,032
Isoform 4 (MMIG-1d) [UniParc].

Checksum: 9F8A2ABC9CAE7004
Show »

FASTA82995,710

References

« Hide 'large scale' references
[1]"Induction of PYPAF1 during in vitro maturation of mouse mast cells."
Kikuchi-Yanoshita R., Taketomi Y., Koga K., Sugiki T., Atsumi Y., Saito T., Ishii S., Hisada M., Suzuki-Nishimura T., Uchida M.K., Moon T.-C., Chang H.-W., Sawada M., Inagaki N., Nagai H., Murakami M., Kudo I.
J. Biochem. 134:699-709(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), SUBCELLULAR LOCATION.
Strain: BALB/cJ.
[2]"Structural, expression, and evolutionary analysis of mouse CIAS1."
Anderson J.P., Mueller J.L., Rosengren S., Boyle D.L., Schaner P., Cannon S.B., Goodyear C.S., Hoffman H.M.
Gene 338:25-34(2004) [PubMed] [Europe PMC] [Abstract]
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]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"Cryopyrin activates the inflammasome in response to toxins and ATP."
Mariathasan S., Weiss D.S., Newton K., McBride J., O'Rourke K., Roose-Girma M., Lee W.P., Weinrauch Y., Monack D.M., Dixit V.M.
Nature 440:228-232(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[9]"Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3."
Kanneganti T.-D., Oezoeren N., Body-Malapel M., Amer A., Park J.-H., Franchi L., Whitfield J., Barchet W., Colonna M., Vandenabeele P., Bertin J., Coyle A., Grant E.P., Akira S., Nunez G.
Nature 440:233-236(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[10]"Novel role of PKR in inflammasome activation and HMGB1 release."
Lu B., Nakamura T., Inouye K., Li J., Tang Y., Lundbaeck P., Valdes-Ferrer S.I., Olofsson P.S., Kalb T., Roth J., Zou Y., Erlandsson-Harris H., Yang H., Ting J.P., Wang H., Andersson U., Antoine D.J., Chavan S.S., Hotamisligil G.S., Tracey K.J.
Nature 488:670-674(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EIF2AK2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF486632 mRNA. Translation: AAL90874.1.
AY495376 mRNA. Translation: AAS75794.1.
AY495377 mRNA. Translation: AAS75795.1.
AY337285 mRNA. Translation: AAR03540.1.
AY337292 expand/collapse EMBL AC list , AY337286, AY337287, AY337288, AY337289, AY337290, AY337291 Genomic DNA. Translation: AAR03541.1.
AY337299 expand/collapse EMBL AC list , AY337293, AY337294, AY337295, AY337296, AY337297, AY337298 Genomic DNA. Translation: AAR03542.1.
AY337306 expand/collapse EMBL AC list , 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.
RefSeqNP_665826.1. NM_145827.3.
XP_006532920.1. XM_006532857.1.
XP_006532921.1. XM_006532858.1.
XP_006532922.1. XM_006532859.1.
UniGeneMm.54174.

3D structure databases

ProteinModelPortalQ8R4B8.
SMRQ8R4B8. Positions 3-92.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-60132N.
IntActQ8R4B8. 1 interaction.

PTM databases

PhosphoSiteQ8R4B8.

Proteomic databases

PaxDbQ8R4B8.
PRIDEQ8R4B8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000079476; ENSMUSP00000078440; ENSMUSG00000032691. [Q8R4B8-1]
ENSMUST00000101148; ENSMUSP00000098707; ENSMUSG00000032691. [Q8R4B8-1]
GeneID216799.
KEGGmmu:216799.
UCSCuc007jeh.1. mouse. [Q8R4B8-1]

Organism-specific databases

CTD114548.
MGIMGI:2653833. Nlrp3.

Phylogenomic databases

eggNOGNOG82860.
GeneTreeENSGT00740000115159.
HOGENOMHOG000294064.
HOVERGENHBG063656.
InParanoidQ8R4B8.
KOK12800.
OMASKQEREH.
OrthoDBEOG7P5T07.
PhylomeDBQ8R4B8.

Enzyme and pathway databases

ReactomeREACT_98458. Immune System.

Gene expression databases

ArrayExpressQ8R4B8.
BgeeQ8R4B8.
CleanExMM_NLRP3.
GenevestigatorQ8R4B8.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR001611. Leu-rich_rpt.
IPR003590. Leu-rich_rpt_RNase_inh_sub-typ.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF02758. PYRIN. 1 hit.
[Graphical view]
SMARTSM00368. LRR_RI. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEPS50824. DAPIN. 1 hit.
PS51450. LRR. 5 hits.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio375328.
PROQ8R4B8.
SOURCESearch...

Entry information

Entry nameNALP3_MOUSE
AccessionPrimary (citable) accession number: Q8R4B8
Secondary accession number(s): Q1JQ87, Q1JQ88, Q6JEL0
Entry history
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: June 1, 2002
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot