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UniProtKB - Q96P20 (NLRP3_HUMAN)

UniProt

Q96P20 - NLRP3_HUMAN

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Protein

NACHT, LRR and PYD domains-containing protein 3

Gene

NLRP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. 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, beta-amyloid fibers, environmental or industrial particles and nanoparticles, etc. However, it is unclear what constitutes the direct NLRP3 activator. 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 (By similarity). 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 (By similarity).By similarity1 Publication1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi226 – 2338ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • peptidoglycan binding Source: HGNC
  • sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • apoptotic process Source: UniProtKB
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • defense response Source: HGNC
  • defense response to virus Source: Ensembl
  • detection of biotic stimulus Source: HGNC
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • interleukin-18 production Source: Ensembl
  • interleukin-1 beta production Source: Ensembl
  • interleukin-1 secretion Source: Ensembl
  • negative regulation of acute inflammatory response Source: BHF-UCL
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of interleukin-1 beta secretion Source: BHF-UCL
  • negative regulation of NF-kappaB import into nucleus Source: HGNC
  • negative regulation of NF-kappaB transcription factor activity Source: HGNC
  • NLRP3 inflammasome complex assembly Source: Ensembl
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: HGNC
  • positive regulation of interleukin-13 production Source: Ensembl
  • positive regulation of interleukin-1 beta secretion Source: HGNC
  • positive regulation of interleukin-4 production Source: UniProtKB
  • positive regulation of interleukin-5 production Source: Ensembl
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of T-helper 17 cell differentiation Source: Ensembl
  • positive regulation of T-helper 2 cell cytokine production Source: UniProtKB
  • positive regulation of T-helper 2 cell differentiation Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of type 2 immune response Source: UniProtKB
  • protein oligomerization Source: HGNC
  • signal transduction Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-844456. The NLRP3 inflammasome.

Names & Taxonomyi

Protein namesi
Recommended name:
NACHT, LRR and PYD domains-containing protein 3
Alternative name(s):
Angiotensin/vasopressin receptor AII/AVP-like
Caterpiller protein 1.1
Short name:
CLR1.1
Cold-induced autoinflammatory syndrome 1 protein
Cryopyrin
PYRIN-containing APAF1-like protein 1
Gene namesi
Name:NLRP3
Synonyms:C1orf7, CIAS1, NALP3, PYPAF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:16400. NLRP3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB-SubCell
  • NLRP3 inflammasome complex Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Inflammasome, Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Familial cold autoinflammatory syndrome 1 (FCAS1)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold. Rarely, some patients may also develop late-onset renal amyloidosis.
See also OMIM:120100
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001V → M in FCAS1 and MWS. 4 Publications
Corresponds to variant rs121908147 [ dbSNP | Ensembl ].		VAR_013227
Natural varianti262 – 2621R → W in FCAS1 and MWS; spontaneous polymerization into inflammasome speck. 3 Publications
VAR_014104
Natural varianti307 – 3071L → P in FCAS1 and MWS. 2 Publications
Corresponds to variant rs180177431 [ dbSNP | Ensembl ].		VAR_014124
Natural varianti355 – 3551L → P in FCAS1. 1 Publication
Corresponds to variant rs28937896 [ dbSNP | Ensembl ].		VAR_043685
Natural varianti441 – 4411A → V in FCAS1. 1 Publication
Corresponds to variant rs121908146 [ dbSNP | Ensembl ].		VAR_013229
Natural varianti490 – 4901R → K in FCAS1. 1 Publication
Corresponds to variant rs145268073 [ dbSNP | Ensembl ].		VAR_043689
Natural varianti525 – 5251F → C in FCAS1. 1 Publication
Corresponds to variant rs180177478 [ dbSNP | Ensembl ].		VAR_031853
Natural varianti629 – 6291E → G in FCAS1. 1 Publication
Corresponds to variant rs121908148 [ dbSNP | Ensembl ].		VAR_013230
Muckle-Wells syndrome (MWS)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary periodic fever syndrome characterized by fever, chronic recurrent urticaria, arthralgias, progressive sensorineural deafness, and reactive renal amyloidosis. The disease may be severe if generalized reactive amyloidosis occurs.
See also OMIM:191900
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001V → M in FCAS1 and MWS. 4 Publications
Corresponds to variant rs121908147 [ dbSNP | Ensembl ].		VAR_013227
Natural varianti262 – 2621R → W in FCAS1 and MWS; spontaneous polymerization into inflammasome speck. 3 Publications
VAR_014104
Natural varianti305 – 3051D → N in CINCA and MWS; spontaneous polymerization into inflammasome speck. 6 Publications
Corresponds to variant rs121908153 [ dbSNP | Ensembl ].		VAR_014105
Natural varianti307 – 3071L → P in FCAS1 and MWS. 2 Publications
Corresponds to variant rs180177431 [ dbSNP | Ensembl ].		VAR_014124
Natural varianti350 – 3501T → M in MWS and CINCA; spontaneous polymerization into inflammasome speck. 4 Publications
Corresponds to variant rs151344629 [ dbSNP | Ensembl ].		VAR_014366
Natural varianti354 – 3541A → V in MWS. 1 Publication
Corresponds to variant rs121908149 [ dbSNP | Ensembl ].		VAR_013228
Natural varianti441 – 4411A → T in MWS. 1 Publication
Corresponds to variant rs180177430 [ dbSNP | Ensembl ].		VAR_014369
Natural varianti571 – 5711G → R in MWS. 1 Publication
Corresponds to variant rs121908151 [ dbSNP | Ensembl ].		VAR_014107
Chronic infantile neurologic cutaneous and articular syndrome (CINCA)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare congenital inflammatory disorder characterized by a triad of neonatal onset of cutaneous symptoms, chronic meningitis, and joint manifestations with recurrent fever and inflammation.
See also OMIM:607115
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti174 – 1741I → T in CINCA. 1 Publication
Corresponds to variant rs180177449 [ dbSNP | Ensembl ].		VAR_043679
Natural varianti262 – 2621R → L in CINCA. 1 Publication
Corresponds to variant rs180177442 [ dbSNP | Ensembl ].		VAR_043680
Natural varianti262 – 2621R → P in CINCA. 1 Publication
Corresponds to variant rs180177442 [ dbSNP | Ensembl ].		VAR_043681
Natural varianti266 – 2661L → H in CINCA. 1 Publication
Corresponds to variant rs180177436 [ dbSNP | Ensembl ].		VAR_043682
Natural varianti305 – 3051D → G in CINCA. 1 Publication
Corresponds to variant rs180177447 [ dbSNP | Ensembl ].		VAR_043683
Natural varianti305 – 3051D → N in CINCA and MWS; spontaneous polymerization into inflammasome speck. 6 Publications
Corresponds to variant rs121908153 [ dbSNP | Ensembl ].		VAR_014105
Natural varianti308 – 3081Q → K in CINCA. 1 Publication
Corresponds to variant rs180177432 [ dbSNP | Ensembl ].		VAR_043684
Natural varianti311 – 3111F → S in CINCA. 2 Publications
Corresponds to variant rs121908154 [ dbSNP | Ensembl ].		VAR_014106
Natural varianti350 – 3501T → M in MWS and CINCA; spontaneous polymerization into inflammasome speck. 4 Publications
Corresponds to variant rs151344629 [ dbSNP | Ensembl ].		VAR_014366
Natural varianti356 – 3561E → D in CINCA. 1 Publication
Corresponds to variant rs180177444 [ dbSNP | Ensembl ].		VAR_043686
Natural varianti360 – 3601H → R in CINCA. 1 Publication
Corresponds to variant rs180177434 [ dbSNP | Ensembl ].		VAR_014367
Natural varianti407 – 4071T → P in CINCA. 1 Publication
Corresponds to variant rs180177445 [ dbSNP | Ensembl ].		VAR_043687
Natural varianti438 – 4381T → I in CINCA. 1 Publication
Corresponds to variant rs180177433 [ dbSNP | Ensembl ].		VAR_043688
Natural varianti438 – 4381T → N in CINCA. 1 Publication
Corresponds to variant rs180177433 [ dbSNP | Ensembl ].		VAR_014368
Natural varianti525 – 5251F → L in CINCA. 1 Publication
Corresponds to variant rs180177439 [ dbSNP | Ensembl ].		VAR_043690
Natural varianti572 – 5721Y → C in CINCA. 2 Publications
Corresponds to variant rs180177438 [ dbSNP | Ensembl ].		VAR_043691
Natural varianti575 – 5751F → S in CINCA. 1 Publication
Corresponds to variant rs121908152 [ dbSNP | Ensembl ].		VAR_014108
Natural varianti634 – 6341L → F in CINCA. 1 Publication
Corresponds to variant rs180177446 [ dbSNP | Ensembl ].		VAR_043692
Natural varianti664 – 6641M → T in CINCA. 1 Publication
Corresponds to variant rs180177435 [ dbSNP | Ensembl ].		VAR_014370
Natural varianti861 – 8611Y → C in CINCA. 1 Publication
Corresponds to variant rs180177452 [ dbSNP | Ensembl ].		VAR_023551

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi15 – 151E → R: Complete loss of PYCARD filament nucleation. 1 Publication
Mutagenesisi22 – 232LK → PA: Loss of PYCARD-binding. No effect on GBP5-binding. 1 Publication
Mutagenesisi23 – 231K → E: Complete loss of PYCARD filament nucleation; when associated with E-24. 1 Publication
Mutagenesisi24 – 241K → E: Complete loss of PYCARD filament nucleation; when associated with E-23. 1 Publication
Mutagenesisi27 – 271M → E: Complete loss of PYCARD filament nucleation. 1 Publication
Mutagenesisi43 – 431R → W: Complete loss of PYCARD filament nucleation. 1 Publication
Mutagenesisi64 – 641E → R: Complete loss of PYCARD filament nucleation. 1 Publication
Mutagenesisi82 – 821D → R: Complete loss of PYCARD filament nucleation. 1 Publication

Keywords - Diseasei

Amyloidosis, Deafness, Disease mutation

Organism-specific databases

MalaCardsiNLRP3.
MIMi120100. phenotype.
191900. phenotype.
607115. phenotype.
Orphaneti93365. CINCA syndrome with NLRP3 mutations.
47045. Familial cold urticaria.
575. Muckle-Wells syndrome.
PharmGKBiPA26512.

Chemistry

ChEMBLiCHEMBL1741208.
GuidetoPHARMACOLOGYi1770.

Polymorphism and mutation databases

BioMutaiNLRP3.
DMDMi262527566.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10361036NACHT, LRR and PYD domains-containing protein 3PRO_0000080886Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi8 ↔ 108Redox-active1 Publication

Post-translational modificationi

The disulfide bond in the pyrin domain might play a role in reactive oxygen species-mediated activation.1 Publication
Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Ubiquitination does not lead to degradation, but inhibits inflammasome activation (By similarity). 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.By similarity1 Publication

Keywords - PTMi

Disulfide bond, Ubl conjugation

Proteomic databases

EPDiQ96P20.
PaxDbiQ96P20.
PeptideAtlasiQ96P20.
PRIDEiQ96P20.

PTM databases

iPTMnetiQ96P20.
PhosphoSiteiQ96P20.

Expressioni

Tissue specificityi

Predominantly expressed in macrophages. Also expressed in dendritic cells, B- and T-cells (at protein level) (PubMed:11786556) (PubMed:17164409). Expressed in LPS-treated granulocytes, but not in resting cells (at protein level) (PubMed:17164409). Expression in monocytes is very weak (at protein level) (PubMed:17164409). Expressed in stratified non-keratinizing squamous epithelium, including oral, esophageal and ectocervical mucosa and in the Hassall's corpuscles in the thymus. Also, detected in the stratified epithelium covering the bladder and ureter (transitional mucosa) (at protein level) (PubMed:17164409). Expressed in chondrocytes (PubMed:12032915). Expressed at low levels in resting osteoblasts (PubMed:17907925).4 Publications

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), and by TNF (PubMed:14662828). Up-regulated in osteoblasts after exposure to invasive, but not invasion-defective, strains of Salmonella typhimurium (at protein level) (PubMed:17907925).2 Publications

Gene expression databases

BgeeiENSG00000162711.
GenevisibleiQ96P20. HS.

Organism-specific databases

HPAiCAB009190.
HPA012878.
HPA017374.

Interactioni

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 DAPIN/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 (PubMed:24630722). NLRP3 localizes at the end of each PYCARD filament (PubMed:24630722). Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization (PubMed:24630722). 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 (PubMed:24630722). 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 (PubMed:24630722). Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:17431422) (PubMed:26347139). Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). 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 leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction (PubMed:23430110). Directly interacts with IRF4 (via the LRR domain); this interaction is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T-cells (By similarity).By similarity2 Publications9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAVSQ7Z4344EBI-6253230,EBI-995373
PYCARDQ9ULZ38EBI-6253230,EBI-751215

GO - Molecular functioni

Protein-protein interaction databases

BioGridi125319. 48 interactions.
DIPiDIP-41153N.
IntActiQ96P20. 36 interactions.
MINTiMINT-230535.
STRINGi9606.ENSP00000337383.

Chemistry

BindingDBiQ96P20.

Structurei

Secondary structure

1
1036
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 1510Combined sources
Helixi19 – 3012Combined sources
Beta strandi34 – 374Combined sources
Helixi43 – 486Combined sources
Helixi51 – 6212Combined sources
Helixi64 – 7714Combined sources
Helixi81 – 899Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QF2X-ray1.70A/B3-112[»]
ProteinModelPortaliQ96P20.
SMRiQ96P20. Positions 5-110.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9393PyrinPROSITE-ProRule annotationAdd
BLAST
Domaini220 – 536317NACHTPROSITE-ProRule annotationAdd
BLAST
Repeati742 – 76221LRR 1Add
BLAST
Repeati771 – 79222LRR 2Add
BLAST
Repeati799 – 81921LRR 3Add
BLAST
Repeati828 – 84922LRR 4Add
BLAST
Repeati856 – 87621LRR 5Add
BLAST
Repeati885 – 90622LRR 6Add
BLAST
Repeati913 – 93321LRR 7Add
BLAST
Repeati942 – 96322LRR 8Add
BLAST
Repeati970 – 99122LRR 9Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi690 – 6978Poly-Glu

Domaini

The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD-binding.1 Publication
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 similarity1 Publication

Sequence similaritiesi

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

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IE5X. Eukaryota.
ENOG4111H3D. LUCA.
GeneTreeiENSGT00840000129675.
HOVERGENiHBG063656.
InParanoidiQ96P20.
KOiK12800.
OMAiNCHRVES.
OrthoDBiEOG091G01CG.
PhylomeDBiQ96P20.
TreeFamiTF340267.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR029495. NACHT-assoc.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF14484. FISNA. 1 hit.
PF13516. LRR_6. 4 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01288. FISNA. 1 hit.
SM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q96P20-1) [UniParc]FASTAAdd to basket

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
MKMASTRCKL ARYLEDLEDV DLKKFKMHLE DYPPQKGCIP LPRGQTEKAD 
        60         70         80         90        100
HVDLATLMID FNGEEKAWAM AVWIFAAINR RDLYEKAKRD EPKWGSDNAR 
       110        120        130        140        150
VSNPTVICQE DSIEEEWMGL LEYLSRISIC KMKKDYRKKY RKYVRSRFQC 
       160        170        180        190        200
IEDRNARLGE SVSLNKRYTR LRLIKEHRSQ QEREQELLAI GKTKTCESPV 
       210        220        230        240        250
SPIKMELLFD PDDEHSEPVH TVVFQGAAGI GKTILARKMM LDWASGTLYQ 
       260        270        280        290        300
DRFDYLFYIH CREVSLVTQR SLGDLIMSCC PDPNPPIHKI VRKPSRILFL 
       310        320        330        340        350
MDGFDELQGA FDEHIGPLCT DWQKAERGDI LLSSLIRKKL LPEASLLITT 
       360        370        380        390        400
RPVALEKLQH LLDHPRHVEI LGFSEAKRKE YFFKYFSDEA QARAAFSLIQ 
       410        420        430        440        450
ENEVLFTMCF IPLVCWIVCT GLKQQMESGK SLAQTSKTTT AVYVFFLSSL 
       460        470        480        490        500
LQPRGGSQEH GLCAHLWGLC SLAADGIWNQ KILFEESDLR NHGLQKADVS 
       510        520        530        540        550
AFLRMNLFQK EVDCEKFYSF IHMTFQEFFA AMYYLLEEEK EGRTNVPGSR 
       560        570        580        590        600
LKLPSRDVTV LLENYGKFEK GYLIFVVRFL FGLVNQERTS YLEKKLSCKI 
       610        620        630        640        650
SQQIRLELLK WIEVKAKAKK LQIQPSQLEL FYCLYEMQEE DFVQRAMDYF 
       660        670        680        690        700
PKIEINLSTR MDHMVSSFCI ENCHRVESLS LGFLHNMPKE EEEEEKEGRH 
       710        720        730        740        750
LDMVQCVLPS SSHAACSHGL VNSHLTSSFC RGLFSVLSTS QSLTELDLSD 
       760        770        780        790        800
NSLGDPGMRV LCETLQHPGC NIRRLWLGRC GLSHECCFDI SLVLSSNQKL 
       810        820        830        840        850
VELDLSDNAL GDFGIRLLCV GLKHLLCNLK KLWLVSCCLT SACCQDLASV 
       860        870        880        890        900
LSTSHSLTRL YVGENALGDS GVAILCEKAK NPQCNLQKLG LVNSGLTSVC 
       910        920        930        940        950
CSALSSVLST NQNLTHLYLR GNTLGDKGIK LLCEGLLHPD CKLQVLELDN 
       960        970        980        990       1000
CNLTSHCCWD LSTLLTSSQS LRKLSLGNND LGDLGVMMFC EVLKQQSCLL 
      1010       1020       1030 
QNLGLSEMYF NYETKSALET LQEEKPELTV VFEPSW
Length:1,036
Mass (Da):118,173
Last modified:November 3, 2009 - v3
Checksum:i4C1DFB2B5B283CE8
GO
Isoform 1 (identifier: Q96P20-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     721-777: Missing.
     836-892: Missing.

Show »
Length:922
Mass (Da):105,975
Checksum:i8680FA0F4259B6F8
GO
Isoform 3 (identifier: Q96P20-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     720-1036: Missing.

Show »
Length:719
Mass (Da):83,533
Checksum:i0BF2090304B74886
GO
Isoform 4 (identifier: Q96P20-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     721-777: Missing.

Show »
Length:979
Mass (Da):111,884
Checksum:iDB355ECE3BF0A226
GO
Isoform 5 (identifier: Q96P20-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     836-892: Missing.

Note: No experimental confirmation available.
Show »
Length:979
Mass (Da):112,263
Checksum:i8E46F79B1A816B5E
GO
Isoform 6 (identifier: Q96P20-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     776-796: WLGRCGLSHECCFDISLVLSS → C

Note: No experimental confirmation available.
Show »
Length:1,016
Mass (Da):115,968
Checksum:iCE6980B309C3322D
GO

Sequence cautioni

The sequence AAC39910 differs from that shown. Reason: Frameshift at positions 893, 918 and 926. Curated
The sequence AAL12497 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAL12498 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAL33908 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAL65136 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAD92128 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG37494 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti167 – 1671R → L in AAL78632 (PubMed:12355493).Curated
Sequence conflicti167 – 1671R → L in AAM14669 (PubMed:12355493).Curated
Sequence conflicti167 – 1671R → L in AAL14640 (PubMed:12355493).Curated
Sequence conflicti323 – 3231Q → H in AAL78632 (PubMed:12355493).Curated
Sequence conflicti323 – 3231Q → H in AAM14669 (PubMed:12355493).Curated
Sequence conflicti323 – 3231Q → H in AAL14640 (PubMed:12355493).Curated
Sequence conflicti439 – 4391T → S in AAC39910 (PubMed:11042152).Curated
Sequence conflicti523 – 5231M → V in BAG37494 (Ref. 5) Curated
Sequence conflicti599 – 5991K → M in AAC39910 (PubMed:11042152).Curated
Sequence conflicti617 – 6171K → N in AAL78632 (PubMed:12355493).Curated
Sequence conflicti617 – 6171K → N in AAM14669 (PubMed:12355493).Curated
Sequence conflicti617 – 6171K → N in AAL14640 (PubMed:12355493).Curated
Sequence conflicti622 – 6232QI → HD in AAC39910 (PubMed:11042152).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti174 – 1741I → T in CINCA. 1 Publication
Corresponds to variant rs180177449 [ dbSNP | Ensembl ].		VAR_043679
Natural varianti200 – 2001V → M in FCAS1 and MWS. 4 Publications
Corresponds to variant rs121908147 [ dbSNP | Ensembl ].		VAR_013227
Natural varianti262 – 2621R → L in CINCA. 1 Publication
Corresponds to variant rs180177442 [ dbSNP | Ensembl ].		VAR_043680
Natural varianti262 – 2621R → P in CINCA. 1 Publication
Corresponds to variant rs180177442 [ dbSNP | Ensembl ].		VAR_043681
Natural varianti262 – 2621R → W in FCAS1 and MWS; spontaneous polymerization into inflammasome speck. 3 Publications
VAR_014104
Natural varianti266 – 2661L → H in CINCA. 1 Publication
Corresponds to variant rs180177436 [ dbSNP | Ensembl ].		VAR_043682
Natural varianti305 – 3051D → G in CINCA. 1 Publication
Corresponds to variant rs180177447 [ dbSNP | Ensembl ].		VAR_043683
Natural varianti305 – 3051D → N in CINCA and MWS; spontaneous polymerization into inflammasome speck. 6 Publications
Corresponds to variant rs121908153 [ dbSNP | Ensembl ].		VAR_014105
Natural varianti307 – 3071L → P in FCAS1 and MWS. 2 Publications
Corresponds to variant rs180177431 [ dbSNP | Ensembl ].		VAR_014124
Natural varianti308 – 3081Q → K in CINCA. 1 Publication
Corresponds to variant rs180177432 [ dbSNP | Ensembl ].		VAR_043684
Natural varianti311 – 3111F → S in CINCA. 2 Publications
Corresponds to variant rs121908154 [ dbSNP | Ensembl ].		VAR_014106
Natural varianti350 – 3501T → M in MWS and CINCA; spontaneous polymerization into inflammasome speck. 4 Publications
Corresponds to variant rs151344629 [ dbSNP | Ensembl ].		VAR_014366
Natural varianti354 – 3541A → V in MWS. 1 Publication
Corresponds to variant rs121908149 [ dbSNP | Ensembl ].		VAR_013228
Natural varianti355 – 3551L → P in FCAS1. 1 Publication
Corresponds to variant rs28937896 [ dbSNP | Ensembl ].		VAR_043685
Natural varianti356 – 3561E → D in CINCA. 1 Publication
Corresponds to variant rs180177444 [ dbSNP | Ensembl ].		VAR_043686
Natural varianti360 – 3601H → R in CINCA. 1 Publication
Corresponds to variant rs180177434 [ dbSNP | Ensembl ].		VAR_014367
Natural varianti407 – 4071T → P in CINCA. 1 Publication
Corresponds to variant rs180177445 [ dbSNP | Ensembl ].		VAR_043687
Natural varianti438 – 4381T → I in CINCA. 1 Publication
Corresponds to variant rs180177433 [ dbSNP | Ensembl ].		VAR_043688
Natural varianti438 – 4381T → N in CINCA. 1 Publication
Corresponds to variant rs180177433 [ dbSNP | Ensembl ].		VAR_014368
Natural varianti441 – 4411A → T in MWS. 1 Publication
Corresponds to variant rs180177430 [ dbSNP | Ensembl ].		VAR_014369
Natural varianti441 – 4411A → V in FCAS1. 1 Publication
Corresponds to variant rs121908146 [ dbSNP | Ensembl ].		VAR_013229
Natural varianti490 – 4901R → K in FCAS1. 1 Publication
Corresponds to variant rs145268073 [ dbSNP | Ensembl ].		VAR_043689
Natural varianti525 – 5251F → C in FCAS1. 1 Publication
Corresponds to variant rs180177478 [ dbSNP | Ensembl ].		VAR_031853
Natural varianti525 – 5251F → L in CINCA. 1 Publication
Corresponds to variant rs180177439 [ dbSNP | Ensembl ].		VAR_043690
Natural varianti571 – 5711G → R in MWS. 1 Publication
Corresponds to variant rs121908151 [ dbSNP | Ensembl ].		VAR_014107
Natural varianti572 – 5721Y → C in CINCA. 2 Publications
Corresponds to variant rs180177438 [ dbSNP | Ensembl ].		VAR_043691
Natural varianti575 – 5751F → S in CINCA. 1 Publication
Corresponds to variant rs121908152 [ dbSNP | Ensembl ].		VAR_014108
Natural varianti629 – 6291E → G in FCAS1. 1 Publication
Corresponds to variant rs121908148 [ dbSNP | Ensembl ].		VAR_013230
Natural varianti634 – 6341L → F in CINCA. 1 Publication
Corresponds to variant rs180177446 [ dbSNP | Ensembl ].		VAR_043692
Natural varianti664 – 6641M → T in CINCA. 1 Publication
Corresponds to variant rs180177435 [ dbSNP | Ensembl ].		VAR_014370
Natural varianti705 – 7051Q → K.1 Publication
Corresponds to variant rs35829419 [ dbSNP | Ensembl ].		VAR_043693
Natural varianti861 – 8611Y → C in CINCA. 1 Publication
Corresponds to variant rs180177452 [ dbSNP | Ensembl ].		VAR_023551

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei720 – 1036317Missing in isoform 3. 1 PublicationVSP_005519Add
BLAST
Alternative sequencei721 – 77757Missing in isoform 1 and isoform 4. 6 PublicationsVSP_005520Add
BLAST
Alternative sequencei776 – 79621WLGRC…LVLSS → C in isoform 6. 1 PublicationVSP_053714Add
BLAST
Alternative sequencei836 – 89257Missing in isoform 1 and isoform 5. 6 PublicationsVSP_005521Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF410477 mRNA. Translation: AAL33908.1. Different initiation.
AF427617 mRNA. Translation: AAL33911.1.
AY051117
, AY051112, AY051113, AY051114, AY051115, AY051116, AY056059, AY056060 Genomic DNA. Translation: AAL12497.1. Different initiation.
AY051117
, AY051112, AY051113, AY051114, AY051115, AY051116 Genomic DNA. Translation: AAL12498.1. Different initiation.
AF468522 mRNA. Translation: AAL78632.1.
AF420469 mRNA. Translation: AAL65136.1. Different initiation.
AY092033 mRNA. Translation: AAM14669.1.
AF418985 mRNA. Translation: AAL14640.2.
AK314998 mRNA. Translation: BAG37494.1. Different initiation.
AB208891 mRNA. Translation: BAD92128.1. Different initiation.
AC104335 Genomic DNA. No translation available.
AL606804 Genomic DNA. No translation available.
CH471148 Genomic DNA. Translation: EAW77184.1.
CH471148 Genomic DNA. Translation: EAW77186.1.
BC117211 mRNA. Translation: AAI17212.1.
BC143359 mRNA. Translation: AAI43360.1.
BC143362 mRNA. Translation: AAI43363.1.
BC143363 mRNA. Translation: AAI43364.1.
AY422168 mRNA. Translation: AAQ98889.1.
AF054176 mRNA. Translation: AAC39910.1. Frameshift.
CCDSiCCDS1632.1. [Q96P20-1]
CCDS1633.1. [Q96P20-2]
CCDS44346.1. [Q96P20-5]
CCDS44347.1. [Q96P20-4]
RefSeqiNP_001073289.1. NM_001079821.2. [Q96P20-1]
NP_001120933.1. NM_001127461.2. [Q96P20-5]
NP_001120934.1. NM_001127462.2. [Q96P20-4]
NP_001230062.1. NM_001243133.1.
NP_004886.3. NM_004895.4. [Q96P20-1]
NP_899632.1. NM_183395.2. [Q96P20-2]
XP_011542350.1. XM_011544048.2. [Q96P20-1]
UniGeneiHs.159483.

Genome annotation databases

EnsembliENST00000336119; ENSP00000337383; ENSG00000162711. [Q96P20-1]
ENST00000348069; ENSP00000294752; ENSG00000162711. [Q96P20-2]
ENST00000366496; ENSP00000355452; ENSG00000162711. [Q96P20-5]
ENST00000366497; ENSP00000355453; ENSG00000162711. [Q96P20-5]
ENST00000391827; ENSP00000375703; ENSG00000162711. [Q96P20-4]
ENST00000391828; ENSP00000375704; ENSG00000162711. [Q96P20-1]
GeneIDi114548.
KEGGihsa:114548.
UCSCiuc001icr.4. human. [Q96P20-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

INFEVERS

Repertory of FMF and hereditary autoinflammatory disorders mutations

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF410477 mRNA. Translation: AAL33908.1. Different initiation.
AF427617 mRNA. Translation: AAL33911.1.
AY051117
, AY051112, AY051113, AY051114, AY051115, AY051116, AY056059, AY056060 Genomic DNA. Translation: AAL12497.1. Different initiation.
AY051117
, AY051112, AY051113, AY051114, AY051115, AY051116 Genomic DNA. Translation: AAL12498.1. Different initiation.
AF468522 mRNA. Translation: AAL78632.1.
AF420469 mRNA. Translation: AAL65136.1. Different initiation.
AY092033 mRNA. Translation: AAM14669.1.
AF418985 mRNA. Translation: AAL14640.2.
AK314998 mRNA. Translation: BAG37494.1. Different initiation.
AB208891 mRNA. Translation: BAD92128.1. Different initiation.
AC104335 Genomic DNA. No translation available.
AL606804 Genomic DNA. No translation available.
CH471148 Genomic DNA. Translation: EAW77184.1.
CH471148 Genomic DNA. Translation: EAW77186.1.
BC117211 mRNA. Translation: AAI17212.1.
BC143359 mRNA. Translation: AAI43360.1.
BC143362 mRNA. Translation: AAI43363.1.
BC143363 mRNA. Translation: AAI43364.1.
AY422168 mRNA. Translation: AAQ98889.1.
AF054176 mRNA. Translation: AAC39910.1. Frameshift.
CCDSiCCDS1632.1. [Q96P20-1]
CCDS1633.1. [Q96P20-2]
CCDS44346.1. [Q96P20-5]
CCDS44347.1. [Q96P20-4]
RefSeqiNP_001073289.1. NM_001079821.2. [Q96P20-1]
NP_001120933.1. NM_001127461.2. [Q96P20-5]
NP_001120934.1. NM_001127462.2. [Q96P20-4]
NP_001230062.1. NM_001243133.1.
NP_004886.3. NM_004895.4. [Q96P20-1]
NP_899632.1. NM_183395.2. [Q96P20-2]
XP_011542350.1. XM_011544048.2. [Q96P20-1]
UniGeneiHs.159483.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QF2X-ray1.70A/B3-112[»]
ProteinModelPortaliQ96P20.
SMRiQ96P20. Positions 5-110.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125319. 48 interactions.
DIPiDIP-41153N.
IntActiQ96P20. 36 interactions.
MINTiMINT-230535.
STRINGi9606.ENSP00000337383.

Chemistry

BindingDBiQ96P20.
ChEMBLiCHEMBL1741208.
GuidetoPHARMACOLOGYi1770.

PTM databases

iPTMnetiQ96P20.
PhosphoSiteiQ96P20.

Polymorphism and mutation databases

BioMutaiNLRP3.
DMDMi262527566.

Proteomic databases

EPDiQ96P20.
PaxDbiQ96P20.
PeptideAtlasiQ96P20.
PRIDEiQ96P20.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336119; ENSP00000337383; ENSG00000162711. [Q96P20-1]
ENST00000348069; ENSP00000294752; ENSG00000162711. [Q96P20-2]
ENST00000366496; ENSP00000355452; ENSG00000162711. [Q96P20-5]
ENST00000366497; ENSP00000355453; ENSG00000162711. [Q96P20-5]
ENST00000391827; ENSP00000375703; ENSG00000162711. [Q96P20-4]
ENST00000391828; ENSP00000375704; ENSG00000162711. [Q96P20-1]
GeneIDi114548.
KEGGihsa:114548.
UCSCiuc001icr.4. human. [Q96P20-1]

Organism-specific databases

CTDi114548.
GeneCardsiNLRP3.
HGNCiHGNC:16400. NLRP3.
HPAiCAB009190.
HPA012878.
HPA017374.
MalaCardsiNLRP3.
MIMi120100. phenotype.
191900. phenotype.
606416. gene.
607115. phenotype.
neXtProtiNX_Q96P20.
Orphaneti93365. CINCA syndrome with NLRP3 mutations.
47045. Familial cold urticaria.
575. Muckle-Wells syndrome.
PharmGKBiPA26512.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE5X. Eukaryota.
ENOG4111H3D. LUCA.
GeneTreeiENSGT00840000129675.
HOVERGENiHBG063656.
InParanoidiQ96P20.
KOiK12800.
OMAiNCHRVES.
OrthoDBiEOG091G01CG.
PhylomeDBiQ96P20.
TreeFamiTF340267.

Enzyme and pathway databases

ReactomeiR-HSA-844456. The NLRP3 inflammasome.

Miscellaneous databases

GeneWikiiNALP3.
GenomeRNAii114548.
PROiQ96P20.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162711.
GenevisibleiQ96P20. HS.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR004020. DAPIN.
IPR011029. DEATH-like_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR029495. NACHT-assoc.
IPR007111. NACHT_NTPase.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF14484. FISNA. 1 hit.
PF13516. LRR_6. 4 hits.
PF02758. PYRIN. 1 hit.
[Graphical view]
SMARTiSM01288. FISNA. 1 hit.
SM01289. PYRIN. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF52540. SSF52540. 2 hits.
PROSITEiPS50824. DAPIN. 1 hit.
PS50837. NACHT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNLRP3_HUMAN
AccessioniPrimary (citable) accession number: Q96P20
Secondary accession number(s): A0A024R5Q0
, B2RC97, B7ZKS9, B7ZKT2, B7ZKT3, O75434, Q17RS2, Q59H68, Q5JQS8, Q5JQS9, Q6TG35, Q8TCW0, Q8TEU9, Q8WXH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: November 3, 2009
Last modified: September 7, 2016
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.