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Q8R4B8

- NALP3_MOUSE

UniProt

Q8R4B8 - NALP3_MOUSE

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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

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

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ8R4B8.
CleanExiMM_NLRP3.
ExpressionAtlasiQ8R4B8. baseline and differential.
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.
GeneTreeiENSGT00770000120466.
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

        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
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:
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
, 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:
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
, 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 ENSGT00770000120466.
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

Bgeei Q8R4B8.
CleanExi MM_NLRP3.
ExpressionAtlasi Q8R4B8. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 123 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